Polymers for additive manufacturing

ABSTRACT

Porous and microporous parts prepared by additive manufacturing as disclosed herein are useful in medical and non-medical applications. The parts are prepared from a composition containing both a solvent soluble component and a solvent insoluble component. After a part is printed by an additive manufacturing process it is exposed to solvent to extract solvent soluble component away from the printed part, resulting in a part having surface cavities.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a national phase application under 35 U.S.C. § 371of International Application No. PCT/US2018/049250, filed Aug. 31, 2018,which claims the benefit under 35 U.S.C. § 119(e) of U.S. ProvisionalPatent Application No. 62/553,377 filed Sep. 1, 2017; which applicationsare incorporated herein by reference in their entireties for allpurposes.

FIELD OF THE INVENTION

The present invention relates generally to additive printing, polymericcompositions for use therein and products made thereby, includingbioabsorbable polymers for medical uses.

BACKGROUND

Additive manufacturing, also known as 3D printing, has developed fromcuriosity to industrial process over the past twenty years, mostlythrough advancements in equipment and computer software. While theability to create advanced structures has improved, there exists a needfor improved, multifunctional materials to support this growingtechnology.

One popular method of additive manufacturing is fused filamentfabrication (FFF). The majority of additive manufacturing through FFFutilizes a single-phase thermoplastic polymeric monofilament to generatea print line through melt extrusion. In advanced scenarios, multiplemonofilaments are used to create zones of specific design. Mostcommonly, a second monofilament is used to generate a support, where thesecond monofilament material is water soluble for easy removal after theprinting is complete. This is quite useful, but the phase organizationof this approach is limited to the tolerances of the printing equipment.

There thus remains a need in the art for improved materials that may beused in additive manufacturing, particularly in the manufacturing ofbiomedical products. The present invention is directed to addressingthis need.

All of the subject matter discussed in the Background section is notnecessarily prior art and should not be assumed to be prior art merelyas a result of its discussion in the Background section. Along theselines, any recognition of problems in the prior art discussed in theBackground section or associated with such subject matter should not betreated as prior art unless expressly stated to be prior art. Instead,the discussion of any subject matter in the Background section should betreated as part of the inventor's approach to the particular problem,which in and of itself may also be inventive.

SUMMARY

In brief, the present disclosure provides compositions useful inadditive manufacturing, methods of conducting additive manufacturingthat make use of the compositions of the present disclosure, andproducts made by the additive manufacturing process, and relatedsubjects.

For example, in one embodiment, the present disclosure provides acomposition comprising an additive in a polymer phase, wherein: a) theadditive is soluble in a solvent; b) the polymer phase comprises anorganic polymer and is essentially insoluble in the solvent; c) thecomposition is a solid at temperatures below 25° C. and a viscous fluidwith a Melt Flow Index of 2.5-30 g/10 min at a temperature above a melttemperature of the composition; and d) the composition has a weightpercent of the additive based on the weight of the composition and aweight percent of the polymer phase based on the weight of thecomposition, where the sum of the weight percent of the additive and theweight percent of the polymer phase is greater than 90%.

In one embodiment the additive provides a distributed phase and thepolymer phase is a continuous phase. In this embodiment, the presentdisclosure provides a composition comprising a distributed phase in acontinuous phase, wherein the distributed phase is soluble in a solvent;the continuous phase comprises an organic polymer and is essentiallyinsoluble in the solvent; the composition is a solid at temperaturesbelow 25° C. and a viscous fluid with a Melt Flow Index of 2.5-30 g/10min at a temperature above the melt temperature of the composition; andthe composition has a weight percent of the distributed phase based onthe weight of the composition and a weight percent of the continuousphase based on the weight of the composition, where the sum of theweight percent of the distributed phase and the weight percent of thecontinuous phase is greater than 90%.

Optionally, these compositions may be further characterized by one ormore (e.g., two, or three, or four, etc.) of the following features: thesolvent is water, the composition is in a form that can be used in anadditive manufacturing process, e.g., in the form of a filament, or aspool of filament, where the filament optionally has a diameter of 1-5mm, or the composition is in the form of powder comprising granules; theweight percent of the additive or distributed phase in the compositionis 1-60%; the additive or distributed phase has an average particle sizeof 20-400 microns; the additive or distributed phase comprises aninorganic salt, e.g., an inorganic salt comprising a cation and ananion, where the cation is selected from sodium, potassium and magnesiumand the anion is selected from chloride, bromide, iodide, sulfate,phosphate, carbonate, bicarbonate; the additive or distributed phasecomprises a water-soluble organic compound, e.g., a sugar or an organiccarboxylic acid or a salt thereof; the polymer or continuous phasecomprises a bioabsorbable polymer, e.g., a bioabsorbable polymercomprising segments selected from polyester, polyanhydride,poly(hydroxybutyrate), and polyether; the polymer or continuous phasecomprises a non-bioabsorbable polymer, e.g., a non-bioabsorbable polymerselected from polyethylene, nylon, thermoplastic polyurethane,polypropylene, polyetheretherketone, polyaryletherketone andpolyethylene terephthalate; the composition has little or no residualmonomer, e.g., has residual monomer at a concentration of <2% by weightwhich includes zero residual monomer; the composition has little or noresidual tin, e.g., a tin concentration of <200 ppm, which includes zerotin; the composition has little or no non-tin heavy metals, e.g., anon-tin metal concentration of <50 ppm, which includes zero non-tinheavy metals.

In another embodiment, the present disclosure provides a method ofadditive manufacturing, the method comprising: a) melting a solidcomposition such as described herein, to provide a molten composition,the molten composition comprising either an additive and polymeric phaseor a distributed phase and continuous phase as described herein; b)performing additive manufacturing to form an article from the moltencomposition; and c) contacting the article with a solvent, where theadditive or distributed phase is soluble in the solvent, underconditions which at least partially dissolves the additive ordistributed phase but not the polymer or continuous phase, to form aporous form of the article.

Optionally, this method may be further characterized by one or more(e.g., two, three, four, etc.) of the following features: the solventcomprises water; the solvent is water; the solvent dissolves at least30% of the additive or distributed phase; the solvent dissolves at least80% of the additive or distributed phase; the solid composition ismelted at a temperature within the range of 50−450° C.; the additivemanufacturing process is performed under an atmosphere of <10% relativehumidity; the additive manufacturing method is fused filamentfabrication (FFF); the porous form of the article comprises a pluralityof holes of a maximum cross section of 0.5-50 mm; the composition has adensity and the article has a density, and the article has a density ofless than 85% of the density of the composition; the conditions comprisea temperature of greater than 20° C.; the porous article comprises poresof a maximum cross section of 20-400 microns; the method furthercomprises sterilizing the article, e.g., by a method selected fromtreatment with ethylene oxide, gamma, e-beam, dry heat and steamprocesses; the method further comprises removing residual solvent fromthe article, e.g., such that the residual solvent is less than oneweight percent based on the weight of the porous form of the article.

In another embodiment, the present disclosure provides a method ofadditive manufacturing, the method comprising: a) providing acomposition as described herein, e.g., comprising a distributed phase ina continuous phase as described herein or comprising an additive phasein a polymer phase as described herein; b) extruding the compositioninto a fiber; c) melting the fiber to provide a molten composition, themolten composition comprising either a distributed phase and acontinuous phase or an additive and a polymer phase; d) performingadditive manufacturing to form an article from the molten composition;d) contacting the article with a solvent, where the additive ordistributed phase is soluble in the solvent, under conditions which atleast partially dissolves the additive or distributed phase but not thecontinuous or polymer phase, to form a porous form of the article; ande) removing residual solvent from the porous form of the article suchthat the residual solvent is less than one weight percent based on theweight of the porous form of the article.

Optionally, this method may be further characterized by one or more(e.g., two, three, four, etc.) of the following features: the solventcomprises water; the solvent is water; the solvent dissolves at least30% of the additive or distributed phase; the solvent dissolves at least80% of the additive or distributed phase; the solid composition ismelted at a temperature within the range of 50−450° C.; the additivemanufacturing process is performed under an atmosphere of <10% relativehumidity; the additive manufacturing method is fused filamentfabrication (FFF); the porous form of the article comprises a pluralityof holes of a maximum cross section of 0.5-50 mm; the composition has adensity and the article has a density, and the article has a density ofless than 85% of the density of the composition; the conditions comprisea temperature of greater than 20° C.; the porous article comprises poresof a maximum cross section of 20-400 microns; the method furthercomprises sterilizing the article, e.g., by a method selected fromtreatment with ethylene oxide, gamma, e-beam, dry heat and steamprocesses; the method further comprises removing residual solvent fromthe article, e.g., such that the residual solvent is less than oneweight percent based on the weight of the porous form of the article.

The herein-mentioned and additional features of the present inventionand the manner of obtaining them will become apparent, and the inventionwill be best understood by reference to the following more detaileddescription. All references disclosed herein are hereby incorporated byreference in their entirety as if each was incorporated individually.

This Brief Summary has been provided to introduce certain concepts in asimplified form that are further described in detail below in theDetailed Description. Except where otherwise expressly stated, thisBrief Summary is not intended to identify key or essential features ofthe claimed subject matter, nor is it intended to limit the scope of theclaimed subject matter.

Also provided in this Brief Summary are some exemplary numberedembodiments of the present disclosure; details related to these numberedembodiment are provided in the Detailed Description.

-   -   1. A composition comprising an additive in a polymer phase,        wherein:        -   a. the additive is soluble in a solvent;        -   b. the polymer phase comprises an organic polymer and is            essentially insoluble in the solvent;        -   c. the composition is a solid at temperatures below 25° C.            and a viscous fluid with a Melt Flow Index of 2.5-30 g/10            min at a temperature above the melt temperature of the            composition; and        -   d. the composition has a weight percent of the additive            based on the weight of the composition and a weight percent            of the polymer phase based on the weight of the composition,            where the sum of the weight percent of the additive and the            weight percent of the polymer phase is greater than 90%.    -   2. The composition of embodiment 1 where the solvent is water.    -   3. The composition of embodiment 1 in a form that can be used in        an additive manufacturing process, e.g., FFF, such as a powder        or fiber.    -   4. The composition of embodiment 1 in a form of a filament.    -   5. The composition of embodiment 4 wherein the filament has a        diameter of 1-5 mm.    -   6. The composition of embodiment 1 in the form of a granule.    -   7. The composition of embodiment 1 wherein the weight percent of        the additive in the composition is 1-60%.    -   8. The composition of embodiment 1 wherein the additive has an        average particle size of 20-400 microns.    -   9. The composition of embodiment 1 wherein the additive        comprises an inorganic salt.    -   10. The composition of embodiment 1 wherein the additive        comprises an inorganic salt comprising a cation and an anion,        where the cation is selected from sodium, potassium and        magnesium and the anion is selected from chloride, bromide,        iodide, sulfate, phosphate, carbonate, bicarbonate.    -   11. The composition of embodiment 1 wherein the additive        comprises a water-soluble organic compound.    -   12. The composition of embodiment 11 wherein the water-soluble        organic compound is a sugar.    -   13. The composition of embodiment 11 wherein the water-soluble        organic compound is an organic carboxylic acid or a salt        thereof.    -   14. The composition of embodiment 1 wherein the polymer phase        comprises a bioabsorbable polymer.    -   15. The composition of embodiment 1 wherein the polymer phase        comprises a bioabsorbable polymer comprising segments selected        from polyester, polyanhydride, poly(hydroxybutyrate), and        polyether.    -   16. The composition of embodiment 1 wherein the polymer phase        comprises a non-bioabsorbable polymer.    -   17. The composition of embodiment 16 wherein the polymer phase        comprises a non-bioabsorbable polymer selected from        polyethylene, nylon, thermoplastic polyurethane, polypropylene,        polyetheretherketone, polyaryletherketone and polyethylene        terephthalate.    -   18. The composition of embodiment 1 comprising residual monomer        at a concentration of <2% by weight.    -   19. The composition of embodiment 1 comprising tin at a        concentration of <200 ppm.    -   20. The composition of embodiment 1 comprising one or more heavy        metal excluding tin, at a concentration of <50 ppm.    -   21. A method of additive manufacturing, the method comprising:        -   a. melting a solid composition to provide a molten            composition, the molten composition comprising an additive            and a polymer phase according to any of embodiments 1-20;        -   b. performing additive manufacturing to form an article from            the molten composition; and        -   c. contacting the article with a solvent, where the additive            is soluble in the solvent, under conditions which at least            partially dissolves the additive but not the polymer phase,            to form a porous form of the article.    -   22. The method of embodiment 21 wherein the solvent comprises        water.    -   23. The method of embodiment 21 wherein the solvent is water.    -   24. The method of embodiment 21 wherein the solvent dissolves at        least 30% of the added additive.    -   25. The method of embodiment 21 wherein the solvent dissolves at        least 80% of the added additive    -   26. The method of embodiment 21 wherein the solid composition is        melted at a temperature of 50-450° C.    -   27. The method of embodiment 21 wherein the additive        manufacturing process is performed under an atmosphere of <10%        relative humidity.    -   28. The method of embodiment 21 wherein the additive        manufacturing method is fused filament fabrication (FFF).    -   29. The method of embodiment 21 wherein the porous form of the        article comprises a plurality of holes of a maximum cross        section of 0.5-50 mm.    -   30. The method of embodiment 21 wherein the composition has a        density and the article has a density, and the article has a        density of less than 85% of the density of the composition.    -   31. The method of embodiment 21 wherein the conditions comprise        a temperature of greater than 20° C.    -   32. The method of embodiment 21 wherein the porous article        comprises pores of a maximum cross section of 20-400 microns.    -   33. The method of embodiment 21 further comprising sterilizing        the article by a method selected from treatment with ethylene        oxide, gamma, e-beam, dry heat and steam processes.    -   34. The method of embodiment 21 further comprising removing        residual solvent from the article such that the residual solvent        is less than one weight percent based on the weight of the        porous form of the article.    -   35. A method of additive manufacturing, the method comprising:        -   a. providing a composition comprising an additive in a            polymer phase according to any of embodiments 1-20;        -   b. extruding the composition into a fiber;        -   c. melting the fiber to provide a molten composition, the            molten composition comprising an additive and a polymer            phase;        -   d. performing additive manufacturing to form an article from            the molten composition;        -   e. contacting the article with a solvent, where the additive            is soluble in the solvent, under conditions which at least            partially dissolves the additive but not the polymer phase,            to form a porous form of the article; and        -   f. removing residual solvent from the porous form of the            article such that the residual solvent is less than one            weight percent based on the weight of the porous form of the            article.

The details of one or more embodiments are set forth in the descriptionbelow. The features illustrated or described in connection with oneexemplary embodiment may be combined with the features of otherembodiments. Thus, any of the various embodiments described herein canbe combined to provide further embodiments. Aspects of the embodimentscan be modified, if necessary to employ concepts of the various patents,applications and publications as identified herein to provide yetfurther embodiments. Other features, objects and advantages will beapparent from the description, the drawings, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary features of the present disclosure, its nature and variousadvantages will be apparent from the accompanying drawings and thefollowing detailed description of various embodiments. Non-limiting andnon-exhaustive embodiments are described with reference to theaccompanying drawings in which:

FIG. 1 shows five different exemplary phase morphologies for an additivewithin a polymer phase, e.g., a distributed phase within a continuousphase.

FIG. 2 provides an SEM image of a printed article.

FIGS. 3A and 3B provide SEM images of a printed article before (FIG. 3A)and after (FIG. 3B) solvent extraction.

FIGS. 4A and 4B show histograms of pore directionality for printedarticles before (FIG. 4A) and after (FIG. 4B) solvent extraction.

FIGS. 5A, 5B, 5C and 5D provide SEM images of printed articles aftersolvent extraction.

FIG. 6 is a photograph showing the wicking performance of two parts thatwere each printed with PDO/PEG (60/40).

FIG. 7 is a photograph showing the wicking performance of two parts, oneprinted with PDO/PEG (60/40) and the other printed with HDPE/PCL(45/55).

FIG. 8 provides SEM images of 3D printed parts that have been exposed todegradation conditions.

FIG. 9 is a graph of estimated accelerated time in vitro (days) vs.amount of degradation, for 3D printed parts having various compositions.

DETAILED DESCRIPTION

The present invention may be understood more readily by reference to thefollowing detailed description of preferred embodiments of the inventionand the Examples included herein.

Briefly stated, the present disclosure provides methods for additiveprinting, polymeric compositions for use therein, and products madethereby, including products having porosity or microporosity, i.e.,porosity that is greater than that created by the additive printingprocess itself. Thus, the present disclosure provides compositionsuseful in additive manufacturing, methods of conducting additivemanufacturing that make use of the compositions of the presentdisclosure, and products made by the additive manufacturing process, andrelated subjects.

Porous and microporous parts prepared by additive manufacturing asdisclosed herein are useful in medical and non-medical applications. Theparts are prepared from a composition containing both a solvent solublecomponent and a solvent insoluble component. After a part is printed byan additive manufacturing process it is exposed to solvent to extractsolvent soluble component away from the printed part, resulting in apart having an altered surface morphology.

As one exemplary application, the compositions and related methods areuseful in the production of medical devices, such as devices that willcontact the body of a patient, either internally or externally. Thepresent disclosure provides compositions and methods that facilitate theability to create customized, patient specific implants with increasedand precision designs. The compositions and methods of the presentdisclosure support the creation of advanced scaffolds, artificialpartial or complete organs, targeted pharmaceutical delivery, and manyother applications.

The present disclosure provides compositions useful for forming parts byadditive manufacturing processes. The compositions will contain at leasttwo components, where one of the components is essentially insoluble ina selected solvent while the other component is substantially soluble inthe selected solvent. Thus, when the composition is immersed orotherwise exposed to the selected solvent for a period of time, one ofthe components will dissolve in the solvent while the other componentwill not dissolve in the solvent. The process whereby the composition isexposed to the selected solvent will be referred to herein as theextraction step or extraction process.

It is not necessary that the relatively insoluble component becompletely insoluble in the solvent, however that component should beessentially insoluble in the solvent during the extraction process. Asused herein, essentially insoluble means that no more than 5 wt % of theinsoluble component dissolves in the solvent during the period of timeof solvent exposure, and in embodiments no more than 4 wt %, or no morethan 3 wt %, or no more than 2 wt %, or no more than 1 wt % of therelatively insoluble component will dissolve in the solvent during theextraction step.

Likewise, it is not necessary that all of the relatively solublecomponent of the composition dissolves in the selected solvent duringthe extraction process. However, the soluble component should dissolvein the solvent much more readily than does the insoluble component, sothat little or no insoluble component dissolves in the solvent duringthe time which the soluble component is dissolving in the solvent.

The soluble component may be referred to herein as the additive, or theadditive component, or the additive phase. The insoluble component maybe referred to herein as the matrix, or the matrix phase. In oneembodiment, the soluble component is the minor component of thecomposition (<50 wt %) and the insoluble component is the majorcomponent (>50 wt %). Thus, the insoluble component may be referred toherein as providing or being the continuous phase while the insolublecomponent may be referred to as providing or being the discontinuousphase.

In one embodiment, the component which is relatively insoluble in theselected solvent will be a polymer, e.g., an organic polymer. Thiscomponent may be a single polymer, e.g., polyethylene or polylactide, orit may be a blend of polymers, e.g., a blend containing polyethylene andpolylactide. In one embodiment, the insoluble component is a singlepolymer composition. Thus, the present discloses a compositioncomprising an additive in a polymer phase, where the additive is solublecomponent of the composition and is soluble in a solvent while thepolymer phase is the insoluble component of the composition andcomprises an organic polymer and is essentially insoluble in thesolvent.

The compositions of the present disclosure include a component that issoluble in a selected solvent, where this component may be referred toas the additive phase. Exemplary materials from which to make anadditive phase include organic small molecules, organic polymers, andinorganic particles. Suitable organic small molecules includes sugarsand carboxylic acids including salts thereof. Suitable organic polymersinclude polyesters and polyanhydrides. Suitable inorganic particlesinclude inorganic salts such as sodium chloride and hydroxyapatite.

In one embodiment, the component which is soluble in the selectedsolvent will be a polymer, e.g., an organic polymer. In anotherembodiment, the component which is soluble in the selected solvent willbe a salt. In either case, this soluble component may be referred to asthe additive component of the composition, or the additive phase.

Optionally, the component which is relatively soluble in the selectedsolvent will be a polymer, for example, an organic polymer. This solublecomponent may be a single polymer, e.g., polyethylene glycol orpolyvinylalcohol, or it may be a blend of polymers, e.g., a blendcontaining polyethylene glycol and polyvinylalcohol. In one embodiment,the soluble component is a single polymer. In one embodiment, thesoluble component is a blend of two or more polymers. In one embodiment,the soluble component is or includes polyalkylene glycol, e.g.,polyethylene glycol (PEG), blends of PEG and polypropylene glycol (PPG)as found in PLURONICS polymers from Dow Du Pont (Midland, Mich.), or PPGwhich may be dissolved in an alcohol solvent such as methanol, while thepolymer phase, which is the insoluble component, is a biodegradablepolymer such as a polymer including polyester and/or polyanhydridesegments, e.g., segments produced from glycolide (polyglycolide, PGA),lactide (polylactide, PLA), dioxanone (polydioxanone, PDO), trimethylenecarbonate (polytrimethylene carbonate, TMC), caprolactone(polycaprolactone, PCL), hydroxyalkanoates such as hydroxybutyrate(polyhydroxyalkanoate, e.g., PHB), or mixtures thereof such aspolylactide-co-glycolide (PLGA).

The additive phase may be formed from an organic polymer that has littleor no solubility in water. An example of such an additive phase ispolylactide which has a solubility in water of less than 0.1 g/L. In oneembodiment, the additive phase is insoluble in water, or essentiallyinsoluble in water having a solubility of less than 1 g/L, or less than0.5 g/L or less than 0.1 g/L.

A polymer phase in the composition, whether present as the soluble orthe insoluble component, or present in both, may be entirelybiodegradable or comprise biodegradable components. However, the polymerphase is not necessarily biodegradable and in another embodiment thepolymer phase is non-biodegradable. In one embodiment, the polymer phasecomprises a mixture of biodegradable and non-biodegradable materials.Exemplary biodegradable polymers include polyesters and polyanhydrides.In one embodiment the biodegradable polymer comprises polyestersegments, such as those derived from glycolide, lactide, dioxanone,trimethylene carbonate, caprolactone, citric acid, hydroxyalkanoates,and others.

In one embodiment, the insoluble component of the composition is apolymer phase formed entirely from, or comprising, a non-degradablepolymer. Examples of suitable non-degradable polymers include nylon,polypropylene, polyetheretherketone, polyaryletherketone,polyterephthalate, polyvinylalcohol, polyurethane, thermoplasticpolyurethane (TPU), and polypropylene.

Optionally, when the polymer phase comprises a non-bioabsorbable polymerselected from polyethylene, nylon, thermoplastic polyurethane,polypropylene, polyetheretherketone, polyaryletherketone andpolyethylene terephthalate, the additive is soluble in an organicsolvent such as chloroform while the polymer phase is not soluble in theorganic solvent, e.g., chloroform, and the additive is a polymerincluding polyester and/or polyanhydride segments, e.g., segmentsproduced from glycolide (polyglycolide, PGA), lactide (polylactide,PLA), dioxanone (polydioxanone, PDO), trimethylene carbonate(polytrimethylene carbonate, TMC), caprolactone (polycaprolactone, PCL),hydroxyalkanoates such as hydroxybutyrate (polyhydroxyalkanoate, e.g.,PHB), or mixtures thereof such as polylactide-co-glycolide (PLGA).

Optionally, the component which is relatively soluble in the selectedsolvent is not a polymer. For example, the soluble component may be asalt.

In one embodiment, the additive phase, which may be distributed within apolymer phase, or may contain a polymer phase distributed within theadditive phase, comprises a water soluble inorganic salt. The inorganicsalt is preferably a biocompatible inorganic salt such as sodiumchloride. Sodium chloride is soluble in water at room temperature at alevel of 359 g/L. In one embodiment, the inorganic salt is soluble inwater at room temperature to an extent of at least 100 g/L, or at least200 g/L, or at least 300 g/L.

The composition of the present disclosure comprises a solvent solublecomponent and a solvent insoluble component. Taken together, these twocomponents may comprises 100% by weight of the composition. However, inother embodiments, these two components comprise the majority of thecomposition, i.e., greater than 50% by weight of the composition, or atleast 60 wt %, or at least 70 wt %, or at least 80 wt %, or at least 90wt %, or at least 95 wt % of the total weight of the composition of thepresent disclosure. Thus, in one embodiment the present disclosureprovides a composition comprising an additive in a polymer phase,wherein the additive is soluble in a solvent, the polymer phasecomprises an organic polymer and is essentially insoluble in thesolvent, and the composition has a weight percent of the additive basedon the weight of the composition and a weight percent of the polymerphase based on the weight of the composition, where the sum of theweight percent of the additive and the weight percent of the polymerphase is greater than 90%. As noted previously, the additive may be apolymer or polymer blend, or it may be a salt.

As mentioned herein, in one aspect the present disclosure is acomposition comprising a distributed phase (also referred to as, e.g.,the soluble phase or soluble component) and a continuous phase (alsoreferred to as, e.g., the insoluble phase or insoluble component). Thecomposition is a solid at room temperature, so that it can be formedinto, and hold, a suitable shape such as a granule or filament. However,at an elevated temperature the composition will melt and become capableof flowing. Upon cooling, the composition will return to a solid state.When used in additive manufacturing, the cooled material will providethe shape of the desired printed material. Thus, the composition may bedescribed as thermoplastic. Either one or both of the continuous ordistributed phase may be described as having thermoplastic properties.

Thermoplastic compositions as provided herein for additivemanufacturing, such as FFF printing and other similar melt-extrusionadditive manufacturing processes, can consist of one or multiple phases,depending on the compatibility and solubility of components as well asthe intended manufacturing process. In specific cases, a composition ofthe present disclosure that is useful for additive manufacturing mayinclude one or more continuous phases, and/or one or more distributedphases. For example, the composition may have two continuous phasesformed from two different materials that are immiscible with another.Likewise, the composition may have two distributed phases formed fromtwo different materials that are immiscible with one another. In anotherembodiment, the composition has a single continuous phase formed fromtwo or more materials that are miscible with one another. Similarly, inanother embodiment, the composition has a distributed phase that isformed from two or more materials that may or may not be miscible withone another.

A continuous phase may be identified through the connectivity of a phaseover a certain length. For example, in the instance where the continuousphase comprises a polymer that is electrically conductive, thecontinuous phase allows for current to flow through the continuous phaselength.

A continuous phase can have a non-structured form in which thecontinuous phase has a random form. A continuous phase can take severalforms, including rod structures, foam structures, particulates where theparticulates are contacting each other, film structures, lamellarstructures, fiber-like structures and laminate structures.

As mentioned previously, the continuous phase may be or comprise apolymer, e.g., a thermoplastic polymer. The composition comprising thepolymeric continuous phase will also comprise a distributed phasecomprising a porogen or other additive that has been mixed with thepolymer but maintains a separate phase from the polymeric continuousphase. When a relatively large amount of additive has been combined withthe polymer, the additive may be present in such a large amount that itforms a continuous phase, and the polymer mixed therewith forms adistributed phase within the continuous phase.

In some embodiments, the composition comprises multiple continuousphases. Multiple continuous phases may take the form of continuousfibers within a continuous coating, co-continuous foam-like structures,lamellar structures, side-by-side phases, and other forms. In anexemplary embodiment, the composition comprises two continuous polymericphases, where the composition is optionally in the form of a singlemonofilament, and the two continuous polymeric phases are optionallymade from polyglycolide and polycaprolactone, which take the form of acontinuous polyglycolide coating surrounding one or morepolycaprolactone filaments. The monofilament is printed into a part,e.g., a medial implant, using an additive manufacturing process, such asa FFF process, which retains the phase separation existing in thepolymer format. After implantation, the polyglycolide degrades viahydrolysis within 2 months, leaving a residual structure with the samenet shape provided by the collection of small polycaprolactone fibersand having 50% of the original part weight. This is useful through theprovision of an initial part with high strength and density whichtransitions into a low density, high surface area implant which supportsingrowth of newly forming tissues.

The compositions of the present disclosure are thermoplastic in thatthey are solid at room temperature, may be heated to reach a fluidmolten state, and will return to a solid state upon cooling.

In one embodiment, the compositions of the present disclosure are solidat ambient temperature, e.g., 20-25° C., but fluid at an elevatedtemperature which is the operating temperature of an additivemanufacturing process. Different additive manufacturing process utilizedifferent operating temperatures, which typically fall within the rangeof 50−450° C. In various embodiments, the compositions of the presentdisclosure become fluid at a temperature which may be referred as themelting point of the composition, where depending on the composition,that melting point is greater than about 50° C., or about 75° C., orabout 100° C., or about 125° C., or about 150° C., or about 175° C., orabout 200° C., or about 225° C., or about 250° C., or about 275° C., orabout 300° C., or about 325° C., or about 350° C., or about 375° C., orabout 400° C., or about 425° C., or about 450° C., including rangesthereof. For example, in one embodiment the compositions of the presentdisclosure have a melting point of greater than about 50° C., e.g.,about 50-100° C., or about 50-150° C., or about 50-200 C. In anotherembodiment, the compositions of the present disclosure have a meltingpoint of greater than about 75° C., e.g., about 75-125° C., or about75-150° C., or about 75-175° C., or about 75-200° C., or about 75-225°C. As used herein, a temperature of “about °X”, where X is a statedtemperature, refers to stated temperature X±5° C. of temperature X,i.e., the stated temperature ±5° C. of the stated temperature.

The melting point of a composition of the present disclosure may bemeasured according to ASTM or ISO standardized procedures. For instance,ASTM D7138-16 may be used to determine the melting temperature ofsynthetic fibers. As another example, ASTM D3418 describes the use ofdifferential scanning calorimetry (DSC) to measure melting point.

When the composition is in a molten state, e.g., above its meltingpoint, it may be characterized in terms of its melt flow properties,e.g., its Melt Flow Index (MFI) or Melt Flow Rate (MFR). A useful testto measure the ability for a material to flow is Melt Flow Index (MFI).This test can be applied to viscous fluids comprising crystalline,semicrystalline, or amorphous thermoplastic materials to determine flowrate of a material under a given condition of temperature and pressure,typically provided as a weight (in grams) per time (in minutes) that acertain composition flows through a given orifice size. This test is anon-specific analysis of the ability of a material to flow, and isuseful to determine the effect of temperature or pressure on thecomposition. For FFF and FDM, it is desirable to determine a temperaturerange suitable for generating an MFI value of between about 2.5-30 gramsper 10 minutes, which translates to preferred FFF or FDM processtemperatures for a given composition.

ASTM and ISO publish standardized procedures for measuring melt flow.

See, e.g., ISO 1133, JIS K 7210, ASTM D1238 as general methods. In oneembodiment, melt flow is measured according to ISO-1122-1 Procedure A.In another embodiment, melt flow is measured according to ASTM A1238Procedure A. In another embodiment, melt flow is measured according toISO 1122-2. In another embodiment, melt flow is measured according toASTM D1238. The Instron Company (Norwood, Mass., USA) sells instrumentsthat can be used to measure melt flow according to these procedures,e.g., their CEAST Melt Flow Testers MF10, MF20, and MF30 models. ZwickRoell AG (Ulm, Germany) is another company that manufactures and sellssuitable melt flow testers.

Thus, the compositions of the present disclosure may optionally becharacterized in terms of their MFI. MFI generally corresponds to howviscous the fluid composition is, where a higher MFI is a less viscouscomposition. For additive manufacturing, a wide range of compositionviscosities can be utilized, however, certain MFI values areparticularly suitable and are provided by the compositions of thepresent disclosure. In one embodiment, the compositions of the presentdisclosure have a MFI of about 2.5-30 g/10 min at a temperature abovethe melt temperature of the composition and within the operatingtemperature of the additive manufacturing process, e.g., FFF. In variousembodiments, the compositions of the present disclosure arecharacterized by a MFI in grams, as measured over a 10 minute period, ofabout 2.5-30, or about 2.5-25, or about 2.5-20, or about 2.5-15, orabout 2.5-10, or about 5-30, or about 5-25, or about 5-20, or about5-15, or about 10-30, or about 10-25, or about 10-15, or about 15-30, orabout 15-25, or about 15-20, or about 20-30, or about 25-30. As usedherein, about X-Y grams refers to each of X and Y±10%, e.g., about 2.5refers to 2.25-2.75, while about 30 refers to 27-33 grams.

With an increase in percentage solid distributed phase in thecomposition, the ability for a material to flow is reduced, mirrored bya reduction in MFI value at the same temperature. Various components canserve to increase the viscous flow of a composition, includingplasticizers like oils, surfactants, organic solvents such as water,monomers, low molecular weight polymers, and oligomers. For the latterthree, it is optional to have these remaining in a polymer as unreactedresiduals and their presence may assist in downstream processing likeextrusion or FFF printing.

Thus, in one embodiment, the present disclosure provides a compositioncomprising an additive in a polymer phase, wherein: a) the additive issoluble in a solvent; b) the polymer phase comprises an organic polymerand is essentially insoluble in the solvent; and the composition is asolid at temperatures below 25° C. and a viscous fluid with a Melt FlowIndex of 2.5-30 g/10 min at a temperature above the melt temperature ofthe composition. Optionally, the composition has a weight percent of theadditive based on the weight of the composition and a weight percent ofthe polymer phase based on the weight of the composition, where the sumof the weight percent of the additive and the weight percent of thepolymer phase is greater than 90%.

The additive phase may comprise particulate that is not generallyspherical. For example, non-spherical crystals such as cuboidal sodiumchloride salt may be present in the composition. Thus, the additivephase may comprise structures with aspect ratios greater than 1:1. Incertain cases, longer aspect ratios generated from chopped filamentcould be added in concentrations to act as a reinforcing element toincrease strength or modulus, or improve fatigue resistance. Forexample, chopped filaments with diameter of 5-50μ, e.g., 12 μm and anaspect ratio of between 1000:1 and 10:1, e.g., about 100:1, may be usedto create a fiber-reinforced filament. During processing, an additivephase comprising these filaments will generate loading with filamentsessentially aligned in the process direction, thereby increasingmechanical performance along that direction.

The particulate may vary in size from about 50 nm to 0.5 mm. In oneembodiment, the mean particle size may be 20-400 μm. In anotherembodiment, the mean particle size may be 400-800 μm. Optionally, theparticulates have a broad size distribution with a standard deviation ofthe mean particle size of greater than ±30%. Alternatively, theparticles have a narrow size distribution with a standard deviation ofthe mean particle size of less than ±30%.

In one embodiment, the particulates have a size distribution with astandard deviation of 10% or less. The distributed phase may includeparticulates of a variety of diameters. The distributed phase maycontain a combination of particulates that have distinctly differentsize ranges. In one embodiment, particulates with a mean particle sizeof 20-400 μm are combined with particulates with a mean particle size of400-800 μm.

The desired mean size and size distribution of the particulate can begenerated by various techniques. The size range to be used can beprepared by a crystallization process, a precipitation process, asieving process, a mechanical grinding or milling process, a cutting orchopping process, and extrusion process or a combination of theseprocesses.

In one embodiment, the additive or distributed phase comprises aninorganic salt, e.g., an inorganic salt comprising a cation and ananion, where the cation is selected from sodium, potassium and magnesiumand the anion is selected from chloride, bromide, iodide, sulfate,phosphate, carbonate, bicarbonate. In one embodiment, the additive ordistributed phase comprises a water-soluble organic compound, e.g., asugar or an organic carboxylic acid or a salt thereof.

In one embodiment, the continuous phase comprises a bioabsorbablepolymer, e.g., a bioabsorbable polymer comprising segments selected frompolyester, polyanhydride, poly(hydroxybutyrate), and polyether. In oneembodiment, the continuous phase comprises a non-bioabsorbable polymer,e.g., a non-bioabsorbable polymer selected from polyethylene, nylon,thermoplastic polyurethane, polypropylene, polyetheretherketone,polyaryletherketone and polyethylene terephthalate.

Table A shows the solubility of various polymers in various solvents.The present disclosure provides two phase compositions in a formsuitable for additive manufacturing, which contains a distributed phaseand a continuous phase. The distributed phase may comprise additivesthat are soluble in solvents that do not dissolve the continuous phasewhich comprise polymer. Alternatively, the additive phase may comprisethe bulk of the composition, and the polymer phase is distributed withinthe continuous additive phase. In the Table, PGA stands forpoly(glycolic acid) or poly(glycolide), PLA stands for poly(lactic acid)or poly(lactide), PCL stands for poly(ε-caprolactone), PVA stands forpoly(vinyl alcohol) and PEG stands for poly(ethylene glycol).

TABLE A Suitable Solvent for Suitable for Polymer ExtractionNon-Extraction PGA HFIP, HFA Chlorinated solvents, most organicsolvents, water PLA Chloroform Water, IPA, PCL Acetone, Chloroform,Water, IPA PVA Water Ethanol PEG Water, acetone, alcohols, Nonpolarsolvents chlorinated solvents

In one embodiment, the composition, optionally in filament or granulatedform, is prepared containing polylactide as the polymer phase andpolyvinylalcohol as the additive phase. Optionally, the polymer phase isthe continuous phase. In another option, the polymer phase is thedistributed phase. The weight ratio of polylactide to polyvinylalcoholcan be varied to provide the desired amount of porosity. In oneembodiment, the majority of the composition on a weight basis iscontinuous phase. In optional embodiments, the distributed phaseprovides 10-50%, or 10-40%, or 10-30%, or 10-20%, or 20-50%, or 20-40%,or 20-30%, or 30-50%, or 30-40% or 40-50% of the weight of thecompositions, with the remainder being continuous phase and additives.For example, a part may be prepared from polylactide as the continuousphase and polyvinylalcohol as the distributed phase at a 60:40 ratio inorder to create a tissue scaffold. To generate microporosity within theprinted part, the part may be soaked in an agitated room temperaturewater bath overnight to extract the polyvinylalcohol.

Optionally, a polymer present in a composition of the presentdisclosure, e.g., a polymer present as the insoluble component, containsone or more non-polymeric components. Exemplary non-polymeric componentsinclude antioxidants, stabilizers, viscosity modifiers, extrusion aids,lubricants, plasticizers, colorants and pigments, and activepharmaceutical ingredients. In some cases, such a non-polymericcomponent can contribute to more than one of the above-mentionedfunctions. In various embodiments, the sum of the non-polymericcomponents, on a weight percent basis based on the total weight of thecontinuous phase, is less than 10, or less than 9, or less than 8, orless than 7, or less than 6, or less than 5, or less than 4, or lessthan 3, or less than 2, or less than 1 wt %.

Suitable antioxidants, which may be used to minimize process andthermally induced oxidation include, e.g., primary antioxidants such ashindered phenols, and secondary antioxidants such as thioethers.Suitable antioxidants are biocompatible in the amounts used in thecomposition. For medical applications, biocompatible antioxidants arepreferred, for example Vitamin E.

Suitable colorants, which impart color to the manufactured part, areoptionally biocompatible in the amounts used in the composition. Formedical applications, biocompatible colorants are preferred. Exemplarybiocompatible colorants include D&C Violet #2, D&C Blue #6, D&C Green#6, (Phthalocyaninato(2-)) copper, and others as described in FDA 21 CFRPart 73 and 74. The colorant should be used in an amount effective toachieve the desired appearance, e.g., about at 0.05 wt % of D&C Violet#2 can be used to create violet-colored devices. In one embodiment, thecolorant is an FDA approved colorant present in the composition at aconcentration of 0.1-0.5 wt %, while in other embodiments the colorantconcentration is 0.2-0.5 wt %, or 0.3-0.5 wt %, or 0.4-0.5 wt %. In oneembodiment the colorant concentration does not exceed about 0.5 wt %.

Suitable viscosity modifiers, which typically reduce the viscosity of amolten form of the composition, include oils, low molecular weightpolymers and oligomers, monomers, and solvents. The use of viscositymodifiers reduces the energy requirement to melt the composition andallows for better flow and layer adhesion during the printing process.In one embodiment, PEG with a molecular weight of about 1,000 isincluded in the continuous phase at 0.5 wt %. When the major componentof the continuous phase is poly(lactide), the addition of 0.5 wt % PEGwith molecular weight of 1,000 provides a composition that is able to beprocessed through a FFF process at 15° C. less than a correspondingmonofilament without the viscosity modifier. In one embodiment, thecomposition of the present disclosure contains a viscosity modifierwhich is a polyethylene glycol having a molecular weight of less than5,000, where the viscosity modifier is present in the composition at aconcentration of less than 1 wt % of the composition.

In one aspect, the present disclosure provides a composition comprisinga distributed phase in a continuous phase. The distributed phase isoptionally soluble in a solvent. The continuous phase optionallycomprises an organic polymer and is insoluble or essentially insolublein the solvent. Optionally, the composition is a solid at temperaturesbelow 25° C. and a viscous fluid above its melt temperature. Forexample, upon melting, the composition has a Melt Flow Index of about2.5-30 g/10 min at a temperature above the melt temperature of thecomposition. Optionally, the composition is a solid at temperaturesbelow 25° C. and is a viscous liquid at an elevated temperature. Forexample, at an elevated temperature, the composition has a Melt FlowIndex of about 2.5-30 g/10 min. The elevated temperate may be in therange of 50-450° C., which is typically employed for FFF additivemanufacturing. Optionally, the composition has a weight percent of thedistributed phase based on the weight of the composition and a weightpercent of the continuous phase based on the weight of the composition,where the sum of the weight percent of the distributed phase and theweight percent of the continuous phase is greater than 90%. These andother aspects of the composition are described hereinafter.

In one embodiment, the polymer phase, which may be either the continuousphase or the distributed phase, comprises more than one polymer. Inanother embodiment, the polymers of the polymer phase are non-phaseseparated. In another embodiment, the polymers of the polymer phase canbe phase separated. When the polymer phase comprises more than onepolymer, the two or more polymers may provide different function to thecomposition, where a polymer may provide, e.g., antioxidant performance,enhanced stability to the composition, viscosity modification, an aid tothe extrusion of the composition, lubricant performance, plasticizerperformance, coloration, and biological activity.

In addition to a continuous phase, the compositions of the presentdisclosure which are useful for additive manufacturing include adistributed phase. The distributed phase is identified as anon-continuous inclusion of material into the overall composition andcan comprise one or a variety of geometries. Illustrations of thedistribution of a distributed phase in a continuous phase is shown inthe boxes of FIG. 1 . As mentioned previously, the distributed phase maybe a polymer that is distributed in a non-polymeric continuous phase. Asanother option, the distributed phase may be a porogen or other additivethat is combined with a polymeric phase that forms the continuous phase.Thus, the polymer phase may be the continuous phase, in which case theadditive is the distributed phase, or the additive may be in thecontinuous phase in which case the polymer is in the distributed phase.

Optionally, the additive phase may be in the form of a particulate. Forinstance, in some versions the particulates are identified as amicrosphere with regular and smooth wall surface. These microspheres maybe created, e.g., by emulsion processes or through a variety of othertechniques used to create microspheres. Alternatively, the particulatecould comprise a collection of irregular shaped particulates. Theirregular shaped particulates can comprise particles with smoothsurfaces, rough surfaces or a combination thereof. The particulates maycomprise particles with jagged edges. Irregular shaped particulates maybe generated through a milling technique such as jet milling,cryomilling or ball milling to reduce the particulate size to anapplication-appropriate diameter.

The additive phase, which may be either the continuous phase or thedistributed phase of the composition, may be defined herein by itssolubility in at least one solvent. In one embodiment, the additivephase is soluble in a solvent or solvent system in which the polymerphase has limited solubility. This difference in solubility is helpfulin order to create a structure with immediate or time-delayed porosityor microporosity based on the dissolution and subsequent separation ofthe additive phase from the polymer phase.

In some embodiments, the continuous phase is essentially insoluble inwater, while the distributed phase dissolves or dissociates in water.Through this property, microporous parts may be generated through theselective dissolution of the distributed phase prior to implantation ofthe formed part in a patient. Conversely, it may be beneficial toimplant a formed part containing a soluble distributed phase, where thedistributed phase is released from the implant after the part isimplanted in the patient. The one or more distributed phases and the oneor more continuous phases may be selected such that a distributed phaseis soluble in a solvent while the components of the continuous phase areessentially insoluble in the same solvent.

In another embodiment, the additive phase comprises an organic polymerthat is soluble in an organic solvent, while the polymer phase is anorganic polymer that is not soluble in the same organic solvent. Anexample of such a composition is when the additive phase ispolycaprolactone (PCL). PCL is soluble in chloroform, dichloromethane,carbon tetrachloride, benzene, toluene, cyclohexanone and 2-nitropropaneat room temperature, and has a low but significant solubility inacetone, 2-butanone, ethyl acetate, dimethylformamide and acetonitrile.PCL is insoluble in ethanol, petroleum ether and diethyl ether. Thecomposition may have a polymer phase which is not soluble in one or moreof the listed solvents. For example, although PCL has a low solubilityin acetone, poly(glycolide-block-trimethylene carbonate) is essentiallyinsoluble in acetone. Accordingly, a composition of PCL as a distributedphase in poly(glycolide-block-trimethylene carbonate) as the continuousphase provides a composition of the present disclosure. As anotherexample, a composition of PCL as a continuous phase within whichpoly(glycolide-block-trimethylene carbonate) as the distributed phaseprovides a composition of the present disclosure.

In a preferred embodiment, the distributed phase is stable within thecontinuous phase such that the at least one distributed phase can beincorporated into the at least one continuous phase during a filamentformation process. The phase separation between the continuous anddistributed phases in the solid form should remain stable duringstorage, and throughout subsequent additive manufacturing processes suchthat the phases remain separated through to the final part. After thefinal part is formed, a solvent may be utilized to remove the solubledistributed phase or the part may be implanted to allow for a delayedporosity generation through in situ dissolution.

The distributed phase is preferably chemically compatible with thecontinuous phase. For example, during storage, the distributed phaseshould not cause degradation of the continuous phase, including chaincleavage or oxidation, and the distributed phase should not initiatecross-linking or other chain modification to the continuous phase. Forparts intended for medical applications, each of the continuous anddistributed phases should be biocompatible, and the cellular response tothe presence of the distributed phase, including ions resulting fromdissolution, or byproducts or processing aids which are delivered withthe implanted part as part of the distributed phase should not bephysically or medically harmful to a patient who receives the additivemanufactured implant of the present disclosure.

Compositions comprising a distributed phase and a continuous phase arecharacterized by the separation of distinct phases within thecomposition. In one embodiment, the distributed phase is uniformlydispersed throughout the composition, but in some cases having thedistributed phase located preferentially in one or more area of thecomposition may be advantageous. Additionally, the distributed phasepreferably does not display agglomeration of particulates, but insteadindividual distributed units are surrounded by material from thecontinuous phase. These properties may be obtained by proper selectionof the relative surface free energy, charge, hydrophobicity, density,shape, size, or other cohesive forces of the distributed versus thecontinuous phase.

In various embodiment, the distributed phase is introduced into thecontinuous phase by melt blending. The distributed phase may be added tothe molten continuous phase, or molten continuous phase may be added tothe distributed phase, and upon suitable mixing, a homogenouscomposition is formed. Alternatively, the distributed phase may be addedto the reactants used to form the continuous phase, i.e., the monomerwhich upon polymerization form the continuous phase. This latter optionis suitable so long as the distributed phase does not dissolve in thereaction mixture used to form the continuous phase, but insteaddisperses throughout that reaction mixture.

In other embodiment, the additive phase is introduced to the polymerphase by melt blending. The additive phase may be added to the moltenpolymer phase, or molten polymer phase may be added to the additivephase, and upon suitable mixing, a homogenous composition is formed.Alternatively, the additive phase may be added to the reactants used toform the polymer phase, i.e., the monomer which upon polymerizationforms the polymer phase. This latter option is suitable so long as theadditive phase does not dissolve in the reaction mixture used to formthe polymer phase, but instead disperses throughout that reactionmixture.

Depending on how the continuous and distributed phases are combined, theresulting composition may have the distributed phase located uniformlythroughout the continuous phase, or the distributed phase may be locatedpreferentially in specific regions of the continuous phase. Forinstance, the distributed phase may be present predominantly orexclusively in the outermost part of a filament formed of continuous anddistributed phase.

The present disclosure provides monofilaments that are useful forforming articles by additive manufacturing processes. Thesemonofilaments may be described in various ways, such as shape, weight,and physical properties.

In one embodiment, the monofilament has a circular cross-section, i.e.,the monofilament is round. As such, the monofilament may be described ashaving a diameter. In one embodiment, the diameter of the monofilamentis within the range of 1.5 to 3.5 mm. In one embodiment the diameter is1.75 mm. In another embodiment the diameter is 3.0 mm. In one embodimentthe diameter does not vary by very much along the length of thefilament. For example, the diameter may be selected from a value withinthe range of 1.5-3.5 mm, and the diameter variation is characterized asbeing no more than ±0.1 mm along the length of the monofilament. In oneembodiment, the diameter does not vary by more than 0.1 mm, e.g., thediameter may be described as 3.0±0.1 mm. In another embodiment thediameter does not vary by more than 0.05 mm, e.g., the diameter may bedescribed as 1.75±0.05 mm.

The monofilaments of the present disclosure are useful in additivemanufacturing. In one embodiment the monofilaments are cut into a usefullength, the useful length corresponding to a useful mass. A useful massof monofilament of the present disclosure is about 200-1,500 grams foradditive manufacturing. Parts printed by additive manufacturing may havevarious masses, where it is convenient that a length of monofilamentprovide sufficient mass to produce an entire part, but the length not beso long that the monofilament is kept in the printing machine for a longtime before it is completely consumed. The monofilament in the printingmachine is subject to degradation by, e.g., oxidation and hydrolysis,and so from a stability perspective it is preferred that themonofilament not be in the machine so long that an appreciable amount ofdegradation occurs. In view of these considerations, the presentdisclosure provides a single (unbroken) length of monofilament thatweighs about 200-1,500, while in other embodiments the mass is about800-1,200 grams, or about 1,000 grams, i.e., 950-1050 grams. The presentdisclosure provides a method of forming monofilament that includescutting the monofilament into lengths which each provide a mass of about1,000 grams.

The monofilaments of the present disclosure may be characterized bytheir length. In one embodiment, the length of monofilament is less than500 meters. In one embodiment, the length of monofilament is less than400 meters. In one embodiment the length of monofilament is within therange of 10-500 meters, and in another embodiment the length ofmonofilament is within the range of 10-400 meters. In one embodiment,the monofilament length is 250-350 meters. Monofilament of these lengthsmay be wound around a spool and used in additive manufacturing. A lengthof about 300-400 meters provides a mass of monofilament of about 1 kg.In one embodiment, the compositions, and accordingly the monofilaments,of the present disclosure have a density of about 1.4 g/cm³ andaccordingly a monofilament length of about 250-350 meters is useful forplacing on a spool and is provided according to one embodiment of thepresent disclosure.

A monofilament of the present disclosure may be characterized by itstensile modulus. A suitable Young's modulus is at least 3 MPa and up to4 GPa or more. The lower limit is suitable for manufacturing partshaving a higher elasticity and compliance, which is desired for manyinterfaces and tissue contacting structures. Higher modulus materialsare selected for structural performance in high strength applications.

A monofilament of the present disclosure may be characterized by itscrystallinity. A variety of total material crystallinity may be usefulin various products, with low crystallinity materials typicallyassociated with softer, higher compliance materials such as elastomers.These materials may exhibit a total crystallinity of <5%. Highlycrystalline materials, such as PLLA or PEEK, may be useful in creationof rigid support structures where structural and mechanical strength iscritical.

Another useful characterization of crystallinity is related to thepresence of crystalline orientation along the fiber axis. Mosttypically, structural and textile monofilaments are used as an orientedyarn to maximize tensile strength, which is an important considerationfor the design and utility of a particular monofilament. Orientation isformed after monofilament extrusion through a series of heating andpulling processes to align crystallites along the filament axis (alsoreferred to as “drawing”), thereby increasing the strength and stiffnessof the fiber in that direction, while having a concomitant effect ofreducing mechanical properties in the transverse filament direction. Inone embodiment, the monofilaments of the present disclosure may becharacterized as being “not drawn” or “undrawn” in that they have notgone through a drawing process and therefore do not have the enhancedcrystallinity which is created by a drawing process. There are severaltechniques to measure crystalline orientation, such as wide-angle X-raydiffraction, birefringence, linear dichroism, and in a techniquespecifically useful in fibers, the acoustic velocity, among others.

Acoustic velocity correlates the degree of drawing with relative speedof sound through the filament, reported as an orientation factor (OF).OF is reported in various ways. OF may be measured on a “0” to “1”scale, with “0” indicating no orientation and “1” indicating totalcrystalline orientation. Sometimes OF is reported as a percentage, i.e.,from 0 to 100%, rather than from 0 to 1. In some instances, OF isreported as a multiple of an unoriented sample, e.g., 1.5 times thevelocity of an unoriented control. However, in general, OF is a measureof the degree of molecular orientation or alignment of the polymerchains in a fiber or filament, where a higher number or higherpercentage reflects a higher degree of alignment.

In many textile filaments, orientation factor can and desirably doesexceed 0.75, 0.85, 0.90, and in some cases 0.95. Conversely,monofilaments used in additive manufacturing processes according to thepresent disclosure do not have the same tensile requirements and insteadbenefit from mechanical isotropy, along with a typically lower energytypically required to melt unoriented filaments. In the monofilaments ofthe present disclosure there may be some low degree of orientation as aresult of the extrusion process, but since the monofilament is undrawn,the orientation factor of the monofilament is relatively low, e.g., lessthan 0.50, 0.40, 0.30, 0.20 or 0.10.

A relatively low OF is advantageous for filaments of the presentdisclosure suitable for a melt extrusion process such as FFF becauselower orientation generally means less crystallinity, and that in turnmeans that less heat is needed to convert the monofilament into a liquidstate, and that the heat which is applied to the monofilament can morequickly and efficiently convert a solid filament into a liquid statesuitable for 3D printing. Accordingly, in one embodiment, themonofilament of the present disclosure has an orientation factor of lessthan 50%, while in another embodiment the monofilament has anorientation factor of less than 40%, and in another embodiment themonofilament has an orientation factor of less than 30%, while in yetanother embodiment the monofilament has an orientation factor of lessthan 20%, and in still another embodiment the monofilament has anorientation factor of less than 10%. In each of these embodiments themonofilament may be further characterized as being an undrawnmonofilament.

The monofilaments of the present disclosure may be characterized bytheir flexibility. A monofilament should not be so rigid (inflexible)that it breaks or fractures when it is wound around a spool. Conversely,the monofilament should not be so flexible that it will not move forwardwhen a trailing portion of monofilament is pushed forward. In otherwords, when a length of monofilament is laid flat and in a straight lineon a surface, and the proximal end of the monofilament is pushed in thedirection of the distal end of the monofilament, the distal end of themonofilament should move forward the same distance as the proximal endis pushed forward. If the solid monofilament is too flexible it will nothave the strength to push molten monofilament out of the heatingchamber.

As a measure of the ability of a monofilament to push itself through aprinter, a column buckling test may be performed, where this testmeasures the buckling resistance, also sometimes referred to as thebuckling strength, of the monofilament in response to axial compression.

In a buckling test performed on a filamentous material, the material isplaced in a vertical direction and clamped above and below the region ofthe filament that will be tested for buckling strength. A monofilamentof the present disclosure may be held in place using two lengths ofBowden tube that run along and share a single longitudinal axis, wherethere is a 1 cm gap between an end of one Bowden tube and an end ofanother Bowden tube. A length of monofilament is placed within the twoBowden tubes, providing an interstitial monofilament, such that 1 cm ofinterstitial monofilament which lies between the two tubes isunsupported and exposed to ambient conditions. A Bowden tube is found onmany FFF printing devices, and is a cylinder having an inner diameter ofabout 2.0 mm, where the monofilament having a width of about 1.75 mmneeds to travel through the Bowden tube during the printing process. Amechanical test frame may be employed to move the two pieces of Bowdentubing closer together to thereby observe the effect of axialcompression on the interstitial filament, while capturing load anddisplacement information during the test.

During the buckling test performed on various monofilaments, theresistance (load) increases in the fiber direction until a peak, atwhich point the buckling is so significant that the monofilament bendsand behaves somewhat like a hinge, at which point the load begins todecrease. This transition from resistance to buckling typically occurswithin the first 5 mm of axial compression. After this peak resistanceis reached, it is easier for the filament to kink/bend rather than pushagainst the applied compressive force.

Using the column buckling test, a study was performed usingmonofilaments with good printability in a 3D printing process, as wellas sample materials that either printed poorly or cannot be printed withexisting printers that employ a Bowden tube or operate as direct driveprinters. This test identified a preferred minimum load correlating witha “printable” monofilament, where that value is at least 1 Newton.Monofilaments which exhibit little or no resistance to the movingtogether of the two ends of the Bowden tubes, i.e., measuring less thanabout 1 Newton in this column buckling test, had trouble being utilizedin a printer using a Bowden tube as well as direct drive printers. Thisfailure to adequately perform was due to low filament stiffnessresulting in column buckling and filament misfeeds.

Accordingly, in one embodiment, the monofilament of the presentdisclosure exhibits at least 1 Newton of resistance when tested by acolumn buckling test. The monofilaments of the present disclosure may becharacterized as having a buckling strength of at least 1 Newton. Inanother embodiment, the monofilament of the present disclosure exhibitsat least 1 Newton of resistance when forces are applied along thelongitudinal axis of a 1 cm length of the monofilament. In oneembodiment, a 1 cm length of monofilament of the present disclosure,having a width or diameter of 1.5-3.0 mm, e.g., 1.75±0.05 mm, exhibitsat least 1 Newton of resistance when tested by this column bucklingtest. In another embodiment, a 1 cm length monofilament of the presentdisclosure, having a width or diameter of 1.5-3.0 mm, e.g., 1.75±0.05mm, exhibits at least 1 Newton of resistance when forces are appliedalong the longitudinal axis of a 3 cm or longer length of themonofilament, where the 1 cm length is unconstrained and there is atleast 1 cm of monofilament on either end of the unconstrained 1 cm ofmonofilament, where the unconstrained 1 cm of monofilament resistscompression along its longitudinal axis.

The present disclosure provides articles that may be sold in commerceand which provide the purchaser with convenient access to compositionsusefully employed in additive manufacturing processes. These articlesmay also be referred to as assemblies.

In one embodiment, the monofilament of the present disclosure is woundaround a spool. The spool may be of the type that includes a core thatsupports the monofilament, and two flanges that together function toretain the monofilament on the core. As mentioned herein, themonofilaments of the present disclosure may be cut into lengths thatprovide about 1 kg of monofilaments, where the present disclosureprovides a spool containing this amount of monofilament. In otherembodiments, the spool contains any of the other cut amounts ofmonofilament as discussed herein.

In one embodiment, the monofilament of the present disclosure ispackaged and stored in a non-degradative environment. This isparticularly important for monofilament that contains components thatare susceptible to air- or moisture-induced degradation. Suchmonofilament includes bioabsorbable monofilament, i.e., monofilamentmade from a bioabsorbable material, which are particularly susceptive tomoisture-induced degradation. Whether or not the monofilament isbioabsorbable, it benefits from being stored in an inert atmosphere.Thus, the non-degradative environment may have one or both of controlledmoisture content and controlled oxygen content. In one embodiment thestorage conditions include a dry environment which has a controlledmoisture content, where in various embodiments the moisture content iscontrolled to be less than 1,000 ppm water, or less than 800 ppm water,or less than 600 ppm water, or less than 400 ppm water. The inertenvironment may be achieved by replacing ambient air with anitrogen-enriched atmosphere. As another option, the inert environmentmay be achieved by placing the monofilament into an oxygen-impermeablepackage, and then sealing the package under reduced pressure. Thisapproach also reduces the amount of moisture to which the monofilamentwould otherwise be exposed to during storage. Optionally, a desiccantsuch a packet of silica may be placed inside the packaging along withthe monofilament.

In one embodiment, the present disclosure provides a packagedmonofilament. The packaged monofilament is wound around a spool, and thespool with the monofilament is placed inside a foil pouch. The foilpouch is sealed under reduced pressure, or after replacing the ambientatmosphere with an inert atmosphere (e.g., nitrogen or dry air). Thus,the present disclosure provides a hermetically sealed package, such as afoil pouch, which contains monofilament wound around a spool, the foilpouch having reduced amount of moisture and/or oxygen relative toambient conditions. Optionally, the pouch contains a single spool.Optionally, there is about 1 kg of a single length of monofilament woundaround the single spool.

In other embodiments, the present disclosure provides methods of forminga composition as disclosed herein in a monofilament form, and forming anassembly from a monofilament as disclosed herein. The method of forminga monofilament form of a composition as disclosed herein comprisescombining a solvent soluble component and a component that is notsoluble in the solvent, melting the composition to provide moltencomposition, extruding the molten composition into an undrawnmonofilament form having a diameter of 1-5 mm, e.g., 1.75±0.05 mm, andthen optionally maintaining the undrawn monofilament in an undrawn formand/or sterilizing the undrawn monofilament. The method of forming anassembly from a monofilament as disclosed herein comprises providing acomposition comprising a solvent soluble component and a component thatis not soluble in the solvent, melting the composition to provide moltencomposition, extruding the molten composition into an undrawnmonofilament form having a diameter of 1-5 mm, e.g., 1.75±0.05 mm,sterilizing the undrawn monofilament, wrapping the undrawn monofilamentaround a spool, and packaging the spool and monofilament in an air-tightcontainer, and optionally placing desiccant into the container.

Thus, in one embodiment the present disclosure provides a method offorming a composition in a monofilament form, where the method includes:combining the additive and the polymer phase to form a composition, oralternatively combining a soluble component and an insoluble component,each as described herein, to form a composition; heating the compositionto form a molten composition; and extruding the molten composition toform an undrawn monofilament. The undrawn monofilament may then be usedin an additive manufacturing process as described herein. Optionally,the undrawn monofilament may be sterilized to facilitate its use informing parts for medical applications. Optionally, the undrawnmonofilament may be packaged for commercial sale. For example, theundrawn monofilament may be wound around a spool as described herein,and then placed into a package for storage until the monofilament isready for use. The package may be air-tight so that the monofilament isnot exposed to moisture or oxidative conditions from the atmosphere. Thepackage may be, e.g., a foil pouch, in which case packaging entailsplacing the monofilament into the foil pouch. The monofilament may haveany of the properties as described herein, e.g., composition, diameter,length, color, orientation factor, buckling strength, etc. For instance,the monofilament may be formed from a composition comprising awater-soluble component such as PEG (polyethyleneglycol, the additive)and a bioabsorbable polymer phase such as PDO that is essentiallyinsoluble in water during the time that the additive dissolves in waterafter forming a part therefrom.

Also, in one embodiment, the present disclosure provides a method offorming an assembly, where the method includes: providing a compositioncomprising additive and polymer phase as described herein, to form acomposition, or alternatively providing a composition comprising asoluble component and an insoluble component, each as described herein,the composition being provided in a molten form; extruding the moltenform of the composition to form an undrawn monofilament; winding theundrawn monofilament onto a spool; and packaging the spool withmonofilament wound thereon in, e.g., a foil pouch. The package may beair-right so that the monofilament is not exposed to moisture oroxidative conditions from the ambient atmosphere. The package may be,e.g., a foil pouch, in which case packaging entails placing themonofilament into the foil pouch. The monofilament may have any of theproperties as described herein, e.g., composition, diameter, length,color, orientation factor, buckling strength, etc. For instance, themonofilament may be cut into a length of less than 400 meters when it isplaced on a spool. As another example, the monofilament may be formedfrom a composition comprising a water-soluble component such as PEG(polyethyleneglycol, the additive) and a bioabsorbable polymer phasesuch as PDO that is essentially insoluble in water during the time thatthe additive dissolves in water after forming a part therefrom.

The present disclosure provides methods of additive manufacturing thatemploy the compositions and/or monofilaments and/or assemblies asdisclosed herein.

In one embodiment, the present disclosure provides a method of additivemanufacturing, the method comprising: a) melting a solid composition toprovide a molten composition, the molten composition comprising anadditive phase and a polymer phase as described herein; b) performingadditive manufacturing to form an article from the molten composition;and c) contacting the article with a solvent, where the additive phaseis soluble in the solvent, under conditions which at least partiallydissolves the additive phase but not the polymer phase, to form a porousor microporous form of the article.

The terms porous and microporosity as used herein refer to the openspaces produced in a printed part due to the dissolution of the solublecomponent when the part is exposed to a solvent in which the solublephase is soluble. When the soluble phase is completely removed from theprinted part, the pores will be present in the insoluble component. Theporosity may take the form of open or closed cells. The porosity maytake a fibrous form, also referred to as a microfibrous form, in whichchannels are present in the article. The pores may alternatively bereferred to as cavities or void spaces.

In the method of additive manufacturing, the solid composition may be amonofilament such as described herein. As an alternative, the solidphase may be a powder or granules as described herein. Rather than beingdescribed as containing an additive phase and a polymer phase, thecomposition may be described as containing a solvent-soluble phase orcomponent, and a solvent insoluble phase or component, where the solventinsoluble component is an organic polymer or a blend of organicpolymers. The additive (insoluble) component may be, as two examples, anorganic polymer or a blend of organic polymers as discussed herein, ormay be a salt as also discussed herein.

In the method of additive manufacturing, the solid composition is meltedto provide a molten composition, where the molten composition comprisesthe additive phase and the polymer phase. In order to provide a moltencomposition, the solid composition is heated to a temperature sufficientto melt the composition. As used herein, melting the composition refersto heating the composition to a sufficiently elevated temperature thatthe composition will flow. For example, the composition may be heated toa temperature of 50-450° C. as needed to melt the composition into astate that allows the composition to flow. The composition may be heatedto a temperature which exceeds the temperature necessary to melt thecomposition. Note that it is not necessary that every component of thecomposition is a liquid at the elevated temperature. However, thecomposition as a whole should flow at an elevated temperate (i.e., atemperature above room temperature, e.g., above 50° C.), and thus has aliquid character at an elevated temperature.

When the composition is in the form of a monofilament, the entirety ofthe monofilament will not be placed into a molten state at one time.Rather, an end of the monofilament will be placed into a heatedenvironment and melted to form a molten composition. For example, duringthe additive manufacturing process, the end of the monofilament may bethreaded into a hollow metal cylinder, e.g., the print head, where thewalls of the cylinder are heated to a temperature that causes thefilament inside the cylinder to melt. The adjacent portion of themonofilament, i.e., the adjacent portion which has not yet converted toa molten form, may be pushed into the hollow cylinder, causing themolten form of the composition already in the cylinder to exit thecylinder and deposit into a space where the part is formed. Themonofilaments of the present disclosure have sufficient strength thatthey can be pushed into the hollow cylinder or similar heating chamber.Unlike many types of monofilaments, it is not necessary that themonofilaments of the present disclosure be capable of being pulled ordrawn. The monofilaments of the present disclosure are intended foradditive manufacturing processes wherein the monofilament is pushed orotherwise forced into a hot chamber where it undergoes a phase changefrom a solid to a molten state. The monofilament should be capable ofbeing pushed into this heating chamber, and also be capable of pushingmolten composition out of the chamber.

In the method of additive manufacturing, the molten composition isconverted to a printed part, which may also be named a printed articleor simply an article. This step may be achieved by a fused filamentfabrication method, which is known in the art, and sometimes referred toas FFF 3D printing. This step may be achieved by a fused depositionmodeling method, which is known in the art, and sometimes referring toas FDM 3D printing.

The present disclosure provides a process of additive manufacturing,e.g., 3D printing. Additive manufacturing by Fused Filament Fabrication(FFF) is a polymer melt-facilitated process in which a polymericfilament is fed into a heated nozzle, with the nozzle transferringenergy to the filament enough to allow material to deform and flow. Thisprocess may result in a complete melting of the polymer, but also itcould result in a softening of the material to a level in which it canbe forced out of the nozzle. The key process parameter is that thematerial is able to be transferred through the nozzle and deform duringtransfer into an essentially flattened form as the nozzle moves over asurface.

Preferably, the filament has diameter of about 1.75-3.0 mm and thenozzle has a diameter of about 0.35-0.40 mm. The filament is typicallyapplied at a layer height of between 0.1 mm and 0.3 mm. Depending on theapplication and required part mechanics and accuracy, alternativediameters for the filament and nozzle may be used, with smallerdiameters leading to higher precision parts at the expense of increasedmanufacturing cycle times. In one embodiment, the present disclosureprovides compositions of continuous and distributed phases as describedherein, in filament form, e.g., a spool of filament suitable for use ina FFF process.

Compositions including a continuous and distributed phase can beprocessed in FFF as long as the softened or melted composition can flowthrough the nozzle. For compositions including a distributed phase thatis solid at the processing temperature, the distributed phase dimensionsmust be less than the nozzle diameter in at least one direction. Forexample, in FFF systems using a nozzle diameter of 0.35 mm, particulatethat is essentially spherical must have a diameter less than 0.35 mm,and more preferably less than 0.30 mm to allow for additional continuousphase material to flow with the distributed phase to maintain continuityof the printed article. Additionally, the layer thickness target shouldalso be considered when assessing the dimensions of a solid distributedphase. For target layer thicknesses of 0.20 mm, the solid distributedphase should have at least one dimension less than 0.20 mm, andpreferably less than 0.15 mm to allow for additional continuous phasematerial to create a continuous layer around at least the majority ofthe particulate in the printed article. For printed layer thicknesses ofless than 0.20 mm, a concomitant reduction in the solid dispersed phaseis required.

In some cases where the solid dispersed phase is an elongated structure,such as a chopped fiber, the FFF process typically results in alignmentof the distributed phase along the printing direction. This isparticularly true with longer aspect ratio filaments or with distributedphase diameters of more than 10% of the layer thickness.

Additive manufacturing through fused filament fabrication (FFF) isenabled through the modulation of a variety of material, process, andenvironmental parameters. The appropriateness of these parameters isprimarily defined through the fiber that is used and secondarily by thepart being manufactured. Additive manufacturing using FFF techniques cancreate macroporous structures through the implementation of infillpatterns. This type of feature is imbedded within software and createsgeometrically regular pore patterns such as triangles, squares, andhexagons. These software generated infill patterns are typically2-dimensional in nature and create a single pore pattern thattransverses the build direction of the part. Other software can generatemore complex 3-dimensional porosity based on geometric structures orirregular patterns. Porosity created in this way physically translatesto a printed part through the deposition of FFF filament and isdependent on the accuracy and layer thickness of the printer, which ison the order of 0.1 mm or more. FFF parts can include macroporous poresizes of about 0.5 mm or larger. The present disclosure utilizes twophase material to form a part, where the part may or may not befabricated to include pores.

The present disclosure forms parts from a two-phase material utilizingan additive manufacturing technique such as FFF. In one embodiment, thepresent disclosure imparts pores to an otherwise non-porous part, i.e.,the part as fabricated does not contain pores, however pores are addedto the after-formed part by removal of additive phase from the part.Alternatively, the part is fabricated to contain pores, and the presentdisclosure imparts additional, typically smaller, pores to the finishedfabricated part.

In additive manufacturing, the use of printing temperature, feed rate,and environmental conditions can influence the quality of a manufacturedpart. For thermoplastic resins, temperature is controlled to create afluid which can be extruded through a nozzle. FFF printing utilizes asingle heating zone with a set temperature above the melting point ofthe filament, and an appropriate temperature range may be determined foreach printing material. At the lower end of the temperature range, thefluid has a higher viscosity and may be useful to create parts withhigher accuracy but the adhesion between deposited filaments may beweaker. At higher temperatures, the fluid may allow for improvedadhesion but part accuracy may be impacted due to the increased abilityfor molten plastic to flow after deposition and during cooling.

Feed rate is a secondary control parameter which is influenced by themelt viscosity of the polymer as well as the stiffness of the solidmonofilament input. Pressure is generated in the polymer melt through adrive mechanism which drives the filament through the FFF system, whichis identified by the “feed rate.” This simple mechanism pushes themonofilament into a heated segment of the printer, wherein themonofilament is melted, and extrusion pressure is generated through theresistance of the molten material to flowing through a nozzle. Anincrease in feed rate directly increases the extrusion pressure, andpressures above a certain monofilament-specific level results infilament buckling and/or drive mechanism errors.

To support 3D printing by Fused Filament Fabrication (FFF), the filamentmust meet certain minimum requirements. A set of drive gears is used toconvey the filament at a precise rate through the nozzle, and this driveforce creates pressure which forces the polymer to flow from the printernozzle. There are two types of FFF printer based on drive location. A“direct drive” printer places the drive mechanism immediately above theprinting nozzle which is moved with the nozzle to form the printedarticle. The moving mass is heavier in this case and printing speeds maybe slower, but there is less distance between the drive mechanism andnozzle which benefits softer materials. In contrast, a “Bowden tube”printer places the drive mechanism remotely and connects the two with aflexible tube that is slightly larger in diameter than the printingfilament. There is less mass to move with the print head but thedistance between drive and nozzle can lead to kinking with softerfilaments.

To facilitate the drive mechanism, filament may exhibit a minimum columnstiffness to allow for accurate feeding through the printer. Columnstiffness, from Euler's column stiffness equations, is increased withincreasing Young's Modulus as well as with filament diameter, and isreduced as the length is increased. Furthermore, the deposition rate ofa composition is directly linked to the feed rate of the filamentthrough the drive mechanism, as this is the only mechanism for meteringmaterial through the printer system. Regularity of feed is dependent onconsistent filament diameter, both to maintain a consistent pressurethrough the printing nozzle and to maintain a specified rate ofdeposition.

Standard industrial printers utilize filament diameters of about1.75-3.0 mm, with target diameter tolerance of ±0.05 mm. Alternativefilament diameters have been used, however, with utility based on theability for the material to feed into the system (adequate stiffness).For bioabsorbable polymers, smaller filament sizes may reduce theduration of time for which the polymer is melted, thereby reducing riskof polymer degradation, which may be useful when targeting highprecision printed articles with fine features.

Standard FFF filament has a typically smooth surface, but this is notnecessary to facilitate the printing process. In certain cases, it maybe beneficial for printing filament to have a rough or textured surfaceto assist the drive mechanism to feed material, particularly those thatare much harder or softer than normal. A roughened or textured surfacemay also be a cosmetic effect of the filament preparation process, andreflect the inclusion of secondary phases or components. It is stillcritical, however, for filament to maintain an average diameter tosupport consistent feeding through the FFF printing system.

Filament printing is typically performed in room temperature conditions,so the filament should preferably meet the stiffness requirements at thedrive mechanism through to the point of heating at or near the nozzle.Filament is typically introduced to the drive mechanism at a temperaturebetween 20-25° C. In the case of “Bowden tube” FFF printers, there maybe a transition from room temperature to elevated temperature up toabout 100° C. as the material approaches the feed nozzle, depending onthe material requirements to support printing.

The present disclosure provides compositions, optionally in filament orgranulated form, which may be used in additive manufacturing.Particularly when the composition includes a bioabsorbable component,special environmental controls may be implemented during the printingprocess. For example, humidity may be kept at low levels so as not toprematurely degrade the bioabsorbable polymer and part made therefrom.Environmental temperature also influences parts during the printingprocess through controlling the rate of cooling and crystallization,where warmer temperatures results in slower cooling and slowercrystallization rate. At lower temperatures, parts may cool quicklyresulting in warping and poor layer adhesion. For example, FFF using PLAmay not be possible at 20° C. due to rapid crystallization duringcooling, but increasing the environmental temperature to 30° C. resultsin high quality printed parts. In general, the environmental temperatureshould be set such that full crystallization of the part doesn't occurduring the printing cycle. Similarly, the printing bed should be set ata temperature close to the glass transition temperature of the polymerto allow for good part adhesion to the build surface, stabilizing thepart during the build cycle.

In the method of additive manufacturing, the printed part is contactedwith a solvent, where the additive phase is soluble in the solvent. Thiscontact achieves a complete or partial extraction of the additive fromthe printed part.

A post-formation process of the present disclosure is exposing theprinted part to a solvent that dissolves, extracts or causes degradationof the additive phase while having little or no impact on the materialsthat form the polymer phase. By this process, the printed part acquiresa microporous structure that is advantageous for some medical implants.In one embodiment, the additive phase is the distributed phase of thecomposition, and the polymer phase is the continuous phase of thecomposition. In another embodiment, the additive phase is the continuousphase of the composition and the polymer phase is the distributed phaseof the composition.

In various embodiments, at least 50 wt %, or at least 60 wt %, or atleast 70 wt %, or at least 80 wt %, or at least 90 wt % of the additivephase is extracted from the printed part. In one embodiment, the solventis water, so that the soluble component of the part is soluble in waterwhile the insoluble component of the printed part is not soluble inwater. In one embodiment, the solvent includes water, as well asoptionally including one or more other solvents that are miscible withwater, e.g., methanol or dimethyl sulfoxide (DMSO) or acetone.

In one embodiment, the extraction is performed at room temperature,i.e., about 23° C. However, in one embodiment the extraction takes placeat an elevated temperature. For example, the extraction may take placeat a temperature of about 25-50° C. In embodiments, the extraction takesplace at a temperature within the range of 25-30° C., or 30-35° C., or35-40° C., or 45-50° C., or 50-55° C., or 60-65° C., or 65-70° C., or70-75° C. The extraction occurs at a temperature which is less than themelting temperature of the composition, e.g., at least 10° C., or atleast 15° C., or at least 20° C., or at least 25° C., or at least 30° C.below the melting temperature of the composition.

Optionally, the entirety of the printed part is contacted with thesolvent. However, in one embodiment, only a portion, or multipledistinct portions, of the printed part is contacted with the solvent.For instance, the printed part may be a biodegradable stent, where thedistal end of the stent is exposed to solvent to create porosity ormicroporosity at the distal end of the stent, but the proximal end ofthe stent is not exposed to the solvent and thus does not have the sameporosity or microporosity as does the distal end. With this approach,the distal end of the stent may be expected to degrade more quickly invivo than the proximal end of the stent. The process of the presentinvention thus provide a mechanism to impart selective and controlled invivo degradation to a 3D printed biodegradable medical implant.

The printed part, post-extraction, will have a density which is lessthan the density of the printed part, pre-extraction. This is becausethe overall volume of the part remains constant or essentially constantduring the extraction process, however the extraction of the solublecomponent reduces the total mass of the printed part. In one embodiment,the extraction process achieves at least a 5% reduction in the densityof the printed part, while in other embodiments the extraction processachieves at least a 10%, or at least a 15%, or at least a 20% reductionin the density of the printed part.

Likewise, the printed part, post-extraction, will have a density whichis less than the density of the composition from which the part wasprinted. This is because the printed part will have a volumeapproximately equal to the volume of the composition from which the partwas printed, however the part will have lost some or all of the solublecomponent that is present in the printing composition. In one embodimentthe printing composition has a density and the article has a density,and the article has a density of less than 85% of the density of thecomposition. In other embodiments, the article has a density of lessthan 80%, or less than 75%, or less than 70%, or less than 65%, or lessthan 60%, or less than 50% of the density of the printed part.

The extraction process will dissolve some or all of the solublecomponent, also referred to herein as the additive, away from theprinted part. The post-extraction printed part will have cavities on itssurface that are formed by the dissolution of the soluble phase. Thecavities are referred to herein as pores or micropores, and the printedpart is describing as having porosity or microporosity.

The microporosity is created by removal of additive phase from theprinted part. That microporosity may be in the form of closed cells,i.e., pores that do not connect with one another. However, if a highconcentration of additive phase is present in the composition of thepresent disclosure, then those regions of additive phase may, in someinstances, touch one another, thereby creating larger pores afterremoval of the additive phase. Accordingly, in some embodiments, theprinted parts may have a somewhat interconnected porous structure.

In looking at the surface of the post-extraction printed part, e.g., bySEM, the cavities will be visible. The size of the cavities may bedescribed, herein in one embodiment the cavities have a maximum crosssection of between 0.5 mm and 50 mm. In another embodiment, cavitieswill have a maximum cross section of 20-400 microns, as viewed by SEM.The cavities will not necessarily be circular in appearance, but may beirregularly shaped. For example, the cross section of 0.5-50 mm refersto the maximum distance across the cavity, and is not necessarily astrict diameter.

The cavities may not be of a circular or generally irregular shape, butmay take the form of a series of channels that each run along thelongitudinal axis of the printed thread. The presence of channels on thesurface of a printed part allows for solvent to flow in and along thechannels.

The removal of the additive phase in the presence of a suitable solventmay be assisted by applying sonication during the removal process. Forexample, the printed part may be placed in an ultrasonic bath along witha suitable solvent that dissolves the additive phase but does notdissolve the polymer phase. In this way, a printed part havingmicroporosity can be produced. In one embodiment of the method ofadditive manufacturing, the printed part is contacted with a solvent inthe presence of sonication, where the additive phase is soluble in thesolvent. This contact achieves a complete or partial extraction of theadditive from the printed part.

After being exposed to the solvent, the remaining part may be dried toachieve a solvent-free condition. For example, the remaining part may beplaced under a reduced pressure so that the remaining solventevaporates. The method of additive manufacturing of the presentdisclosure optionally includes a drying operation to remove excesssolvent from the printed extracted part. In one embodiment, the dryingoperation removes residual solvent from the article such that theresidual solvent is less than one weight percent based on the weight ofthe porous form of the article.

After being exposed to the solvent, the remaining part may be exposed tosterilizing conditions. Thus, the additive manufacturing method of thepresent disclosure optionally includes a sterilizing operation tosterilize the post-extraction article by a method selected fromtreatment with ethylene oxide, gamma, e-beam, dry heat and steamprocesses. This operation kills or removes any live bacteria from theprinted part and thus allows the printed part to be used in cases wherea sterile environment is important, e.g., during surgical implantationof the printed part.

Printed parts can be further enhanced via post-formation processing.Exemplary post-formation processing includes annealing, solventsmoothing, sanding, grinding, and cutting to change final shape.

The present disclosure also provides a method comprising:

-   -   a) providing a composition comprising an additive in a polymer        phase, which may also be referred to as a composition comprising        a solvent soluble component (the additive) and a solvent        insoluble component (the polymer phase) as described herein,        which may be in the form of granules;    -   b) extruding the composition into a fiber;    -   c) melting the fiber to provide a molten composition;    -   d) performing additive manufacturing to form an article (which        may also be referred to as a part, or a printed part) from the        molten composition;    -   e) contacting the article with a solvent, where the additive is        soluble in the solvent, under conditions which at least        partially dissolves the additive but not the polymer phase, to        form a porous form of the article; and    -   f) removing solvent from the porous form of the article such        that the residual solvent still associated with the article is        less than one weight percent based on the weight of the porous        form of the article.

The present disclosure provides parts printed by additive manufacturingprocesses and treated by a post-printing treatment process as disclosedherein.

In one embodiment, the present disclosure provides articles whichcontain microporosity, particularly articles that are made by additivemanufacturing and related post-treatment. This is notable particularlyin medical applications, where the potential to create customized,patient specific implants with increased and precision designs maysupport creation of advanced scaffolds, artificial partial or completeorgans, targeted pharmaceutical delivery, and many other applications.In one embodiment, the microporosity take the form of a series ofchannels that each run along the longitudinal axis of the printedthread.

Filaments that contain extractable materials can be useful for a varietyof applications, including tissue engineering, pharmaceutical delivery,selective filtration, and as a precursor for additional surfacemodification. By incorporating a secondary material which isextractable, surface texture and porosity may be generated that wouldnot be possible through a typical printing process. This technique maybe enabled through the use of a solvent, wherein the solvent dissolvesat least one component of the printed part while the at least one othercomponent is essentially insoluble. It is desirable for the componentsto create distinct phases, and preferably to create phases that aresufficiently interconnected to allow for selective extraction.

As just one example, in one embodiment the present disclosure provides aporous structure that may be created as described herein from degradablepolymer, e.g., a degradable polymer that is formed from lactide, suchthat greater than 70 wt %, or greater than 75 wt %, or greater than 80wt %, or greater than 85 wt %, or greater than 90 wt % of the degradablepolymer is formed from lactide. The porous structure can be printed byfused deposition modeling (i.e., be FDM printed) in such a manner thatthe printed structure has more than 20% void space and up to 80% voidspace, e.g., has at least 20%, or at least 30%, or at least 40%, or atleast 50%, or at least 60%, or at least 70%, and up to 30%, or up to40%, or up to 50%, or up to 60%, or up to 70%, or up to 80% void space.The structure or article can be printed such that there areinterconnected pores within the structure. In one embodiment, there isopen porosity with pore sizes ranging between 50 μm and 500 μm, e.g.,the pore size is at least 50 μm, or at least 100 μm, or at least 200 μm,or at least 300 μm, or at least 400 μm and may be as great as 500 μm, or400 μm, or 300 μm, or as great as 200 μm, or as great as 150 μm, or asgreat as 100 μm.

The surface of the printed structure may optionally contain reactivefunctional groups to increase hydrophilicity or to improve surfacecompatibility or bonding with a second material. For example, thesurface of the structure may optionally be modified by using processessuch as plasma treatment, base or acid surface treatment or irradiation(UV, gamma, e-beam). The treated surface may be further functionalizedby grafting a variety of materials such as polyethylene glycol (PEG),poly(vinyl alcohol) [PVA], chitosan, albumin, hyaluronic acid, heparin,growth factors onto the surface of the scaffold.

The porous structure may optionally be loaded with a hydrogel matrixcomprising growth factors, MSCs, or other cell types, where the hydrogelmay optionally be selected from a group that may closely approximate theprinted scaffold, interact with the printed scaffold, ionically bondwith the printed scaffold, or covalently bond with the printed scaffold.The interaction between the hydrogel matrix and the printed scaffold mayresult in improved cellular approximation with the printed scaffold andincreased stability of the hydrogel within the printed scaffold matrix.The hydrogel matrix may comprise, e.g., hyaluronic acid, albumin,chitosan, polyethylene glycol (PEG). Following incorporation of thehydrogel into the porous scaffold, the porous structure functions tocreate and stabilize a desirable shape and protect the hydrogel scaffoldduring early cell proliferation. In one embodiment, thestructure/hydrogel/cell composite scaffold approximates the mechanicalproperties of the desired tissue construct. In one embodiment, as thecellular composite matures, the printed porous structure, which has beenprinted using one or more degradable polymers, and hydrogel may degradeleaving behind only the cellular components and the extracellular matrixproduced by the cells. Optionally, when the scaffold is printed from oneor more non-degradable polymers, all or a portion of the structure mayremain to provide a permanent support. This provides an exemplaryapplication of the compositions and articles of the present disclosure.

For many applications including medical applications, it would be usefulto create discrete phases with varying functionality at a smaller scalethan equipment-only control allows. The present approach, as describedherein, utilizes a composition comprising an additive in a polymerphase, e.g., a distributed phase comprising the additive which isdispersed in a continuous polymer phase, or if sufficient additive ispresent in the composition, the additive may constitute the continuousphase and the polymer phase may provide a distributed phase. Thecomposition may be in a form particularly suitable for an additivemanufacturing process, e.g., in the form of granules that constitute apowder, or in the form of a filament or fiber. This form is thenprocessed and the subsequently printed part is used to generate tailoredphase-modulated structures.

When the composition is in the form of a powder or granules, it may beused in a direct screw extrusion 3D printing process to form an articleor part of interest. In such a process, a mounted mini-extruder isplaced in combination with a 3d printer, which would utilize heat tomelt the powder or granules material into a fluidized bed. As analternative, a direct plunger extraction 3D printing process may be usedto form an article of part of interest. In such a process, a mountedheated cylinder uses heat and pressure to create a fluidized bed andforce it out of the nozzle. This type of printing looks like a heatedsyringe is being used to create the molten composition and expel it intothe bed of the printer to form the article of interest. When thecomposition is in a monofilament form, FFF 3D printing process may beused to form an article or part of interest.

For medical applications, it would be useful to create discrete phaseswith varying functionality at a smaller scale than equipment-onlycontrol allows. An approach to providing these discrete phases, asdescribed fully herein, utilizes the composition and processing of amonofilament or powder, and post-treatment of the subsequent printedpart to generate tailored phase-modulated structures.

The articles that are printed with the compositions disclosed herein maybe useful in medical applications. For instance, after implantation,they may serve as a tissue scaffold, as described elsewhere herein. Theymay be used as topical devices, i.e., placed on the skin surface of asubject. They may be used in dermal applications. They may be used tofill a defect in tissue or bond. They may be used in trauma treatment.These are examples of where medical implants having microporosity areuseful.

The invention has been described broadly and generically herein. Each ofthe narrower species and subgeneric groupings falling within the genericdisclosure also form part of the invention. This includes the genericdescription of the invention with a proviso or negative limitationremoving any subject matter from the genus, regardless of whether or notthe excised material is specifically recited herein.

Exemplary embodiments of the disclosure include: a compositioncomprising an additive in a polymer phase, wherein: a) the additive issoluble in a solvent; b) the polymer phase comprises an organic polymerand is essentially insoluble in the solvent; c) the composition is asolid at temperatures below 25° C. and a viscous fluid with a Melt FlowIndex of 2.5-30 g/10 min at a temperature above the melt temperature ofthe composition; and d) the composition has a weight percent of theadditive based on the weight of the composition and a weight percent ofthe polymer phase based on the weight of the composition, where the sumof the weight percent of the additive and the weight percent of thepolymer phase is greater than 90%. Another exemplary embodiment of thepresent disclosure is a composition comprising a distributed phase in acontinuous phase, wherein the distributed phase is soluble in a solvent;the continuous phase comprises an organic polymer and is essentiallyinsoluble in the solvent; the composition is a solid at temperaturesbelow 25° C. and a viscous fluid with a Melt Flow Index of 2.5-30 g/10min at a temperature above the melt temperature of the composition; andthe composition has a weight percent of the distributed phase based onthe weight of the composition and a weight percent of the continuousphase based on the weight of the composition, where the sum of theweight percent of the distributed phase and the weight percent of thecontinuous phase is greater than 90%.

Optionally, either of these compositions may be further characterized byone or more (e.g., two, or three, or four, etc.) of the followingfeatures: the solvent is or comprises water, the composition is in aform that can be used in an additive manufacturing process, e.g., in theform of a filament, or a filament wound around a spool, where thefilament optionally has a diameter of about 0.5-5 mm, or about 1-5 mm,or about 1.5-5 mm, or about 2-5 mm, or about 2.5-5 mm, or about 0.5-4mm, or about 1-4 mm, or about 1.5-4 mm, or the composition is in theform of granules; the weight percent of the distributed or additivephase in the composition is 1-60%, or 1-50%, or 1-40%, or 1-30%, or1-20% or 5-60%, or 5-50%, or 5-40%, or 5-30%, or 5-20%, or 10-60%, or10-50%, or 10-40%, or 10-30%, or 20-60%, or 20-50%, or 20-40%, or30-60%, or 30-50%, where these percentage ranges are weight of theadditive or distributed phase, divided by the total weight of thecomposition times 100; the distributed phase has an average particlesize of about 20-400 microns, or about 20-300 microns, or about 20-100microns, or about 40-400 microns, or about 40-300 microns, or about40-200 microns, or about 60-400 microns, or 60-300 microns, or 60-200microns, or 100-400 microns, or 100-300 microns, or 100-200 microns,where these micron values refer the average longest distance through aplurality of distributed phases; the additive or distributed phasecomprises an inorganic salt, e.g., an inorganic salt comprising a cationand an anion, where the cation is selected from sodium, potassium andmagnesium and the anion is selected from chloride, bromide, iodide,sulfate, phosphate, carbonate, bicarbonate; the additive or distributedphase comprises a water-soluble organic compound, e.g., a sugar or anorganic carboxylic acid or a salt thereof; the polymer or continuousphase comprises a bioabsorbable polymer, e.g., a bioabsorbable polymercomprising segments selected from polyester, polyanhydride,poly(hydroxybutyrate), and polyether; the polymer or continuous phasecomprises a non-bioabsorbable polymer, e.g., a non-bioabsorbable polymerselected from polyethylene, nylon, thermoplastic polyurethane,polypropylene, polyetheretherketone, polyaryletherketone andpolyethylene terephthalate; the composition has little or no residualmonomer, e.g., has residual monomer at a concentration of <2% by weight,or <1% by weight, or less than 0.5% by weight; the composition haslittle or no residual tin, e.g., a tin concentration of <200 ppm.; thecomposition has little or no non-tin heavy metals, e.g., a non-tin metalconcentration of <50 ppm.

In other embodiments, the present disclosure provides a method ofadditive manufacturing, the method comprising: a) melting a solidcomposition to provide a molten composition, the molten compositioncomprising an additive phase and a polymer phase as described herein; b)performing additive manufacturing to form an article from the moltencomposition; and c) contacting the article with a solvent, where theadditive phase is soluble in the solvent, under conditions which atleast partially dissolves the additive phase but not the polymer phase,to form a porous or microporous form of the article.

The present disclosure provides the following numbered embodiments,which are exemplary and non-limiting of the embodiments provided by thepresent disclosure:

-   -   1. A composition comprising an additive in a polymer phase,        wherein:        -   a. the additive is soluble in a solvent;        -   b. the polymer phase comprises an organic polymer and is            essentially insoluble in the solvent;        -   c. the composition is a solid at temperatures below 25° C.            and a viscous fluid with a Melt Flow Index of 2.5-30 g/10            min at a temperature above 50° C.; and        -   d. the composition has a weight percent of the additive            based on the weight of the composition and a weight percent            of the polymer phase based on the weight of the composition,            where the sum of the weight percent of the additive and the            weight percent of the polymer phase is greater than 90%.    -   2. The composition of embodiment 1 in a form of a monofilament.    -   3. The composition of embodiment 2 wherein the monofilament is        an undrawn monofilament.    -   4. The composition of embodiment 2 wherein the monofilament has        an orientation factor of less than 50%.    -   5. The composition of embodiment 2 wherein the monofilament has        a diameter of 1-5 mm.    -   6. The composition of embodiment 5 wherein the monofilament has        a diameter of 1.75±0.05 mm.    -   7. The composition of embodiment 6 wherein the monofilament has        a column buckling resistance of at least 1 Newton.    -   8. The composition of embodiment 1 in a form of a powder or        granule.    -   9. The composition of embodiment 1 wherein the additive        comprises an inorganic salt.    -   10. The composition of embodiment 1 wherein the additive        comprises a water-soluble organic compound.    -   11. The composition of embodiment 10 wherein the water-soluble        organic compound is polyethylene glycol.    -   12. The composition of embodiment 1 wherein the polymer phase        comprises a bioabsorbable polymer.    -   13. The composition of embodiment 12 wherein the polymer phase        comprises a bioabsorbable polymer comprising segments selected        from polyester, polyanhydride, poly(hydroxybutyrate) and        polyether, where, in one example, the additive may be or may        include polyalkylene glycol, e.g., polyethylene glycol (PEG) or        polypropylene glycol (PPG) or copolymers of ethylene glycol and        propylene glycol, while the polymer phase is a bioabsorbable        polymer such as a polymer including polyester and/or        polyanhydride segments, e.g., segments produced from glycolide        (polyglycolide, PGA), lactide (polylactide, PLA), dioxanone        (polydioxanone, PDO), trimethylene carbonate (polytrimethylene        carbonate, TMC), caprolactone (polycaprolactone, PCL),        hydroxyalkanoates such as hydroxybutyrate (polyhydroxyalkanoate,        e.g., PHB), or mixtures thereof such as polylactide-co-glycolide        (PLGA).    -   14. The composition of embodiment 1 wherein the polymer phase        comprises a non-bioabsorbable polymer.    -   15. The composition of embodiment 14 wherein the polymer phase        comprises a non-bioabsorbable polymer selected from        polyethylene, nylon, thermoplastic polyurethane, polypropylene,        polyetheretherketone, polyaryletherketone and polyethylene        terephthalate, where, in one example, the additive is soluble in        an organic solvent such as chloroform while the polymer phase is        not soluble in the organic solvent, e.g., chloroform, and the        additive is a polymer including polyester and/or polyanhydride        segments, e.g., segments produced from glycolide (polyglycolide,        PGA), lactide (polylactide, PLA), dioxanone (polydioxanone,        PDO), trimethylene carbonate (polytrimethylene carbonate, TMC),        caprolactone (polycaprolactone, PCL), hydroxyalkanoates such as        hydroxybutyrate (polyhydroxyalkanoate, e.g., PHB), or mixtures        thereof such as polylactide-co-glycolide (PLGA).    -   16. The composition of embodiment 1 wherein the weight percent        of the additive in the composition is 1-60%.    -   17. The composition of embodiment 1 where the solvent is water,        the additive is soluble in water and the polymer phase is        insoluble in water.    -   18. An assembly comprising the monofilament of embodiment 2 and        further comprising a spool, where the monofilament is wrapped        around the spool.    -   19. The assembly of embodiment 18 wherein the monofilament on        the spool is enclosed within an air-tight container.    -   20. A method of forming a composition of embodiment 2        comprising:        -   a. combining the additive and the polymer phase to form a            composition;        -   b. heating the composition to form a molten composition;        -   c. extruding the molten composition to form an undrawn            monofilament; and        -   d. sterilizing the undrawn monofilament.    -   21. A method of forming an assembly of embodiment 18 comprising:        -   a. providing a composition according to embodiment 1 in a            molten form;        -   b. extruding the molten form of the composition to form an            undrawn monofilament;        -   c. winding the undrawn monofilament onto a spool; and        -   d. packaging the spool with monofilament wound thereon.    -   22. A method of additive manufacturing, the method comprising:        -   a. melting a solid composition to provide a molten            composition, the molten composition comprising an additive            and a polymer phase according to any of embodiments 1-17;        -   b. performing additive manufacturing to form an article from            the molten composition; and        -   c. contacting the article with a solvent, where the additive            is soluble in the solvent, under conditions which at least            partially dissolves the additive but not the polymer phase,            to form a porous form of the article.    -   23. The method of embodiment 22 wherein the solvent dissolves at        least 50% of the additive.    -   24. The method of embodiment 22 wherein the solid composition is        melted at a temperature of 50-450° C. to form the molten        composition.    -   25. The method of embodiment 22 wherein the additive        manufacturing method is fused filament fabrication (FFF).    -   26. The method of embodiment 22 wherein the porous form of the        article comprises a plurality of channels that run along the        surface of the article in a longitudinal direction compared to        the longitudinal direction of a fibrous form of the molten        composition created during the additive manufacturing process.    -   27. The method of embodiment 22 further comprising sterilizing        the article by a method selected from treatment with ethylene        oxide, gamma, e-beam, dry heat and steam processes.    -   28. The method of embodiment 22 further comprising removing        solvent from the article such that any residual solvent is less        than one weight percent based on the weight of the porous form        of the article.    -   29. A method of additive manufacturing, the method comprising:        -   a. providing a composition comprising an additive in a            polymer phase according to any of embodiments 1-17;        -   b. extruding the composition into a monofilament fiber;        -   c. melting the monofilament fiber to provide a molten            composition;        -   d. performing additive manufacturing to form an article from            the molten composition;        -   e. contacting the article with a solvent, where the additive            is soluble in the solvent, under conditions which at least            partially dissolves the additive but not the polymer phase,            to form a porous form of the article; and        -   f. removing solvent from the porous form of the article such            that any residual solvent is less than one weight percent            based on the weight of the porous form of the article.

The following Examples are offered by way of illustration and not by wayof limitation.

EXAMPLES Example 1 Microfibrous Article Made from Polydioxanone and PEG

Filaments suitable for additive manufacturing were prepared frompolydioxanone (PDO) and polyethyleneglycol (PEG). The quantities of PDOand PEG present in each of the filament are set forth in Table 1. Theselected amounts of PDO and PEG were placed in a jar. The PDO (Poly-Med,Anderson S.C., USA) had a molecular weight such that a dilute solutionin hexafluoro-2-propanol (HFIP) had an inherent viscosity of 1.7 dL/g ata concentration of 0.1 mg polymer/mL solvent. The PEG had an averagemolecular weight of 20 kDa and was obtained from Dow duPont ChemicalCo., Midland Mich., USA. A jar containing the two powders was shaken atroom temperature to achieve a homogeneous appearance, requiring about 1hour. The mixture was dried under reduced pressure.

The mixture was fed into a custom ¾″ barrel diameter extruder equippedwith a 0.584 cc/rev metering pump and extruded through a die. Theresulting fiber was conveyed using a puller attached to the exit of theextruder and simultaneously the fiber was pulled through a water bath toform the monofilament fiber. These conditions resulting in amonofilament fiber having an average filament diameter of 1.75 mm. Thisprocess may be used to make filaments suitable for additivemanufacturing, e.g., filaments having a diameter of 1.5-3.0 mm. Filamentwas collected on spools and stored in a dry, inert environment (nitrogenatmosphere) until time of use. This filament is referred to herein as aprinting filament.

TABLE 1 PDO (wt %) PEG (wt %) Filament Name 100 0 PDO 100 60 40 PDO 6050 50 PDO 50

FDM printing was performed using a HYDRA 640 printer (Hyrel 3D, Atlanta,Ga.) with a modular direct drive print head equipped with a 1.0 mmnozzle, set to a 15 mm/s feed rate with nozzle temperature and bedtemperature at 165° C. and 45° C., respectively. Each printing filamentwas used to print a disc-shaped article of two layers of printingfilament. The disc consisted of a first series of parallel threadsforming a first layer and a second series of parallel threads forming asecond layer printed on top of the first layer, where the second seriesof parallel threads followed a longitudinal direction that wasperpendicular to the longitudinal direction of the threads in the firstseries. This shape can be seen in FIG. 2 . The printing filament had amelt temperature of about 110° C. and was printed at 165° C., so thatwhen molten printing filament was printed to form the second layer, thefirst layer melted slighted and the first and second layers adhered toone another.

In the printed part, each thread had a width of about 0.8 mm. Thus, thisFDM printing process provided a disc with two layers, each layer havinga 0.5 mm layer thickness. Each layer, and the disc as a whole, had arectilinear infill pattern of 80%. The disc had a diameter of 50 mm. AnSEM image of the printed article is shown in FIG. 2 .

Weighed amounts of the printing filaments having the compositionsdescribed in Table 1, and the printed discs made therefrom, were soakedin deionized water at 37° C. for 15 hours, then carefully removed fromthe water bath, dried to constant weight, and then re-weighed todetermine extracted content. Samples were imaged with Scanning ElectronMicroscopy (SEM) to evaluate morphology, and images were furthercharacterized with ImageJ (National Institutes of Health).

Table 2 lists the extracted content (in weight percent based on theoriginal weight of the sample) and the extraction efficiency (the % ofsoluble polymer (PEG) present in the original format that was extracted)for each of the materials and formats tested.

TABLE 2 Feature Alignment Extracted Extraction Standard ContentEfficiency Deviation Material Format wt % % from Mean, ° PDO 100 PrintedPart 1.2%  — 75.9 PDO 60 Filament 31% 78% 15.4 PDO 60 Printed Part 40%100%  15.8 PDO 50 Filament 44% 88% 13.1 PDO 50 Printed Part 46% 92% 14.1

Table 2 shows that a part printed with PDO 100 printing filament lost1.2% of its weight after the soaking process. This serves as a control.When printing filament containing 60 wt % PDO and 40 wt % PEG was usedto print a part, the starting filament lost 78% of the weight of its PEGcomponent during the soaking process, while the part printed from thisprinting filament lost 100% of the weight of its PEG component duringthe soaking process. When a printing filament containing 50 wt % PDO and50 wt % PEG was used to print a part, the starting filament lost 88% ofthe weight of its PEG component during the soaking process, while thepart printed from this printing filament lost 92% of the weight of itsPEG component during the soaking process.

FIG. 3A provides an SEM image of a part printed with PDO 60 printingfilament. The part shown in FIG. 3A has not undergone an extractionprocess. FIG. 3B provides an SEM image of a part printed with PEO 60printing filament, but in contrast to the part shown in FIG. 3A, thepart shown in FIG. 3B has been exposed to an extraction solvent. Asshown in FIG. 3B, dissolution of the PEG from the printed threads leftbehind a series of channels that each run along the longitudinal axis ofthe printed thread. These channels are not seen in the part shown inFIG. 3A. This directionality is quantified using the ImageJ softwarefrom NIH, which provided the histograms in FIG. 4A (corresponding to thepart in FIG. 3A) and in FIG. 4B (corresponding to the part in FIG. 3B).A similar result was seen from soaking of the PDO 50-derived parts. Theparts shown in FIGS. 3A and 3B appear to have wider threads than thethreads shown in the image of FIG. 2 , and the reason is that in FIGS.3A and 3B the printed threads are seen to be right next to one another,without any gap between the threads, thus giving the appearance of awider thread when in fact there are two threads in what appears to beone thread.

FDM printed parts, post water-extraction, exhibited primarily ascontinuous and aligned filaments. In both the PDO 50 and PDO 60materials, filament alignment was in the direction of nozzle path, i.e.along the print axis. The printed parts extracted with high efficiency,meaning that there was very little or no residual soluble PEG left inthe printed part after extraction, and extraction was improved comparedto the extractability of PEG from the filament precursor.

Example 2 Microfibrous Article Made from High Density Polyethylene andPolycaprolactone

Filaments were prepared as described in Example 1, using high densitypolyethylene (HDPE) and polycaprolactone (PCL) as the insoluble andsoluble materials, respectively. HDPE (Dow Chemical) and PCL (Poly-Med,Anderson, S.C. USA), the latter having an inherent viscosity (IV)=1.8g/mL in CHCl₃ were both used without modification. 1.75 mm diameterprinting filament was collected with composition ratios as described inTable 3. The printing filaments were stored in a dry, inert environmentuntil time of use.

TABLE 3 HDPE (wt %) PCL (wt %) Filament Name 100 0 HDPE 100 60 40 HDPE60 45 55 HDPE 45 20 80 HDPE 20 0 100 PCL 100

FDM printing was performed using a HYDRA 640 printer (Hyrel 3D, Atlanta,Ga.) with a modular direct drive print head equipped with either a 0.4mm or 1.0 mm nozzle. The effect of nozzle temperature was evaluated at185° C., 205° C. and 225° C. Each printing filament was printed into theshape of a disc designed with 50% layer thickness to nozzle diameterratio. In other words, each layer was printed to have a thickness equalto ½ the size of the nozzle diameter (the 0.4 mm nozzle made a 0.2 mmthick layer). Each part had a rectilinear infill pattern set at 80%.

Printed discs, along with printing filament, were soaked in chloroformovernight at room temperature, then carefully removed from the solvent,rinsed in chloroform, and dried to constant weight to determineextracted content. HDPE is insoluble in chloroform and PCL is soluble inchloroform. Samples were imaged with Scanning Electron Microscopy (SEM)to characterize part morphology, and images were characterized withImageJ (National Institutes of Health).

Extraction details and images are provided in Table 4 and FIGS. 5A, 5B,5C and 5D. In Table 4, N.D. means not determined.

TABLE 4 Feature Alignment Extracted Extraction Standard ContentEfficiency Deviation Material Format Wt % % from Mean, ° HDPE 100Printed Part 0 N/A N.D. HDPE 60 Filament 40 100 14.0 HDPE 60 PrintedPart 40 100 17.7 HDPE 45 Filament 51  93 22.0 HDPE 45 Printed Part 52-5495-98  9.9 HDPE 20 Filament N.D. N.D. N.D. HDPE 20 Printed Part N.D.N.D. N.D.

The raw material filament (post-extraction) exhibited a combination offiber-like structure and discontinuous segments with little orientation.3D Printed parts from HDPE 45 (55% extractable content), postchloroform-extraction, exhibited varying morphology depending on theprinting parameters.

Printing through a 1.0 mm nozzle (FIGS. 5A and 5B) resulted in a similarmorphology to the raw material filament, and with increased processtemperature (185° C. FIG. 5A; 205° C. FIG. 5B) created finer features.

Printing through a 0.40 mm nozzle (FIGS. 5C and 5D) surprisingly alteredthe final morphology into primarily a continuous, aligned filamentstructure. In this case, a 20° C. process temperature increase (205° C.FIG. 5C; 225° C. FIG. 5D) improved the homogeneity of the filamentstructure.

In all cases, the extractability of PCL from the 3D printed article wasimproved compared to the extractability from the raw material printingfilament. From this, phase separation and microstructure variants arecreated through shear (1.8 mm filament extruded through a 1.0 mm or 0.4mm nozzle) and homogenized with temperature. This is unexpected becausethe process is conducted at a temperature above the melt temperature forall conditions and one would consider temperature to be the primarydriver of phase separation.

Printing filament and the corresponding 3D printed parts made from HDPE20 were not stable after extraction. The high extractable contentresulted in a discontinuous morphology for the insoluble HDPE portion,resulting in the disintegration of the structure into particles of highdensity polyethylene. Table 4 indicates N.D. (not determined) to reflectthis observation.

Example 3 Wicking Articles Made from Microfibrous 3D Printed Articles

Rectangular shapes were isolated from pre-extracted and post-extracteddiscs prepared in Examples 1 and 2. The rectangular shapes haddimensions of 50 mm length×4 mm width×1 mm thickness. The rectangularshapes were evaluated for water wicking ability by dipping parts into asolution of phenol red indicator dissolved into water and observing thetravel of the colored solution through the part. Results are summarizedin Table 5 and FIG. 6 .

TABLE 5 Material Sample Description Wicking Study Results PDO 60 Solidparts, no substantial Very slight surface travel Pre-extraction surfacefeatures of indicator solution PDO 60 Continuous, highly aligned Wickingthrough the Post-extraction microfilament bundles entirety of the partHDPE 45 Solid parts, no substantial No wicking Pre-extraction surfacefeatures HDPE 45 Continuous, highly aligned No wicking Post-extractionmicrofilament bundles

FIG. 6 shows the difference in aqueous wicking performance betweenpre-extracted and post-extracted parts printed from PDO 60. Wicking ofaqueous phenol red Indicator solution through PDO 60 parts, forpre-extracted part (right) and post-extracted part (left), indicatingthe wicking response at approximately 1 minute post-dip. Within the 1minute timeframe, aqueous indicator solution had wicked along theentirety of the post-extracted PDO 60 part (left) while essentially noindicator solution had wicked along the pre-extracted PDO 60 part(right).

FIG. 7 shows a comparison of the wicking performance between twodifferent post-extracted printed parts. In FIG. 7 , there is shown acomparison of the wicking of aqueous phenol red Indicator solutionbetween HDPE 45 (bottom) and PDO 60 (top), 5 minutes after dropsapplied. Within the 5 minute timeframe, no wicking of the indicatorsolution occurred with the HDPE 45 printed part (bottom), however theindicator solution had wicked through the entire length of the PDO 60printed part (top).

The wicking behavior of 3D printed parts is influenced by the surfaceenergy, and therefore solution compatibility, of the part. The wickingbehavior is greatly enhanced by the microstructure created as a resultof the blending, printing and extraction process as disclosed herein.The formation of aligned microfilament structure provides greaterwicking benefit than a part lacking the aligned microfilament feature.

Example 4 Blended Composition with GLYCOPRENE and LACTOPRENE Polymers

Filaments were prepared as described in Example 1, using a GLYCOPRENE™6829 polymer (a glycolide-based copolymer containing 68% glycolide, 29%caprolactone, and 3% trimethylene carbonate, Poly-Med, Anderson S.C.,USA) and LACTOPRENE™ 8411 (a lactide-based copolymer containing 84%1-lactide, 11% caprolactone, and 5% trimethylene carbonate, Poly-Med,Anderson S.C. USA). GLYCOPRENE™ 6829 polymer is a relatively fastdegrading polymer in vivo while LACTOPRENE™ 8411 is a relatively slowdegrading polymer in vivo. The monofilaments had the compositions shownin Table 6, and each had a 1.75 mm diameter. After formation, thefilaments were stored in a dry, inert environment until time of use.

TABLE 6 LACTOPRENE GLYCOPRENE Filament Name 8411 (wt %) 6829 (wt %) Lac100 100 0 Lac 75 75 25 Lac 60 60 40 Lac 50 50 50 Lac 0 0 100

FDM printing was performed using a F360 printer (Fusion3, Greensboro,N.C.) with a Bowden tube print head equipped with a 0.40 mm nozzle. Eachfilamentary material was printed into a 50 mm×1 mm disc as described inExample 1, designed with 50% layer thickness to nozzle diameter ratioand a rectilinear infill pattern set at 80%.

To study the degradation profile and in vitro morphology changes, anaccelerated degradation study was performed by placing printed discsinto a pH 12 phosphate buffer at 50° C. This accelerated modelsignificantly speeds the degradation process of bioabsorbable polymers,thereby reducing the evaluation time from months to days.

Table 7 details the overall part structure retention compared to the “asprinted” disc shape. In Table 7, R means good “as printed” shaperetention, i.e., the printed shape did not change very much if at allduring the degradation study, D means signs of parts losing “as printed”structure, and NR means the part lost its printed structure, where NR1means filament non-adhesion occurred and NR2 means brittle fractureoccurred.

TABLE 7 Time (days) of incubation at 12 pH, 50° C. Material 0 0.25 1 3 6Lac 100 R R R R R Lac 75 R R NR1 NR1 NR1 Lac 60 R R D D D Lac 50 R R R RR Lac 0 R R R R NR2

Samples were analyzed for morphology with SEM and composition by NMRbefore and during the in vitro study to understand performancedifferences between the various blends being studied. Degradation imagesand mass loss details are shown in FIGS. 8 and 9 . In FIG. 8 , SEMimages are shown at 150× magnification. In FIG. 8 , A refers to partsmade from Lac 100, B refers to parts made from Lac 75, C refers to partsmade from Lac 60, D refers to parts made from Lac 50, and E refers toparts made from Lac 0, using the nomenclature adopted in Table 7. FIG. 9is a graph showing the mass loss profiles of 3D printed parts through a12 pH, 50° C. in vitro degradation cycle. The percentage value is thepercent of the total.

3D printed parts from LACTOPRENE 8411 blends exhibited markedlydifferent degradation morphology compared to single component filament.The composition of the blended materials alters the phase separationwithin the 3D printed part. A 50/50 blend with GLYCOPRENE 6829 yields amixed morphology containing some aligned fibers and shorter segments. A60/40 blend yields an aligned filamentous structure upon partialdegradation. A 75/25 blend yields a first ribbon-like structure uponpartial degradation followed by a filamentous structure with furtherdegradation.

Each blend exhibited a different capability in printed shape retentionthrough the degradation cycle, with lower percentages of LACTOPRENE 8411unexpectedly retaining a higher level of “as printed” part shape. Higherratios of LACTOPRENE in the blend resulted in filament non-adhesionduring in vitro degradation, evidenced by the structure “unravelling.”All blended parts changed in physical morphology throughout degradationwhile parts made of only GLYCOPRENE 6829 or LACTOPRENE 8411 exhibitedsurface cracking and embrittlement during the in vitro evaluationperiod.

Example 5 Porous Articles by 3D Printing of Polycaprolactone withDistributed Inorganic Salt

Filaments were prepared as described in Example 1, by blending togetherpolycaprolactone (PCL) homopolymer and NaCl (Sigma Aldrich), with theformer being insoluble in water and the latter having solubility of 1 Min water at 20° C. The materials were blended in an extruder to formmonofilaments having a 1.75 mm diameter, with material ratios asdescribed in Table 8, and then stored in a dry, inert environment untiltime of use.

TABLE 8 Filament Name % PCL % NaCl PCL 100 100 0 PCL 80 80 20 PCL 70 7030 PCL 60 60 40

FDM printing was performed on a HYDRA™ 640 printer (Hyrel 3D, Atlanta,Ga.) into 50 mm diameter discs using a 1.0 mm nozzle at 165° C., withdisc thickness of 0.5 mm and a rectilinear infill at 80%. Filament, aswell as 3D printed articles, were soaked in deionized water for 15 hoursat room temperature and then dried to constant weight to determineextractable content. The articles were imaged by SEM to identify articlemorphology, with results provided in Table 9. Table 9 shows thebiocomponent material initial composition and subsequent extractiontrial results.

TABLE 9 Extractable Extraction Filament Format Content Efficiency PCL100 3D Printed Part 0.4% N.A. PCL 80 Filament 7.9% 40% PCL 80 3D PrintedPart 9.2% 46% PCL 70 Filament 11.6% 39% PCL 70 3D Printed Part 24.5% 82%PCL 60 Filament 13.1% 33% PCL 60 3D Printed Part 26.4% 66%

Water extractions yielded a partial although not complete removal ofloaded salt. Noteworthy is that significantly increased extractionefficiency was observed from the 3D printed parts as compared to thestarting material filament. By SEM analysis, the pores created by saltelution appeared to be disconnected. The appearance of the created poresis consistent with the size and shape of the loaded salt particulate. Ahigher loading of salt (e.g., 50 wt % or more) would be expected tocreate an open-cell porous structure.

The invention has been described broadly and generically herein. Each ofthe narrower species and subgeneric groupings falling within the genericdisclosure also form part of the invention. This includes the genericdescription of the invention with a proviso or negative limitationremoving any subject matter from the genus, regardless of whether or notthe excised material is specifically recited herein.

It is also to be understood that as used herein and in the appendedclaims, the singular forms “a,” “an,” and “the” include plural referenceunless the context clearly dictates otherwise, the term “X and/or Y”means “X” or “Y” or both “X” and “Y”, and the letter “s” following anoun designates both the plural and singular forms of that noun. Inaddition, where features or aspects of the invention are described interms of Markush groups, it is intended, and those skilled in the artwill recognize, that the invention embraces and is also therebydescribed in terms of any individual member and any subgroup of membersof the Markush group, and Applicants reserve the right to revise theapplication or claims to refer specifically to any individual member orany subgroup of members of the Markush group.

All references disclosed herein, including patent references andnon-patent references, are hereby incorporated by reference in theirentirety as if each was incorporated individually.

It is to be understood that the terminology used herein is for thepurpose of describing specific embodiments only and is not intended tobe limiting. It is further to be understood that unless specificallydefined herein, the terminology used herein is to be given itstraditional meaning as known in the relevant art.

Reference throughout this specification to “one embodiment” or “anembodiment” and variations thereof means that a particular feature,structure, or characteristic described in connection with the embodimentis included in at least one embodiment. Thus, the appearances of thephrases “in one embodiment” or “in an embodiment” in various placesthroughout this specification are not necessarily all referring to thesame embodiment. Furthermore, the particular features, structures, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural referents, i.e., one or more,unless the content and context clearly dictates otherwise. It shouldalso be noted that the conjunctive terms, “and” and “or” are generallyemployed in the broadest sense to include “and/or” unless the contentand context clearly dictates inclusivity or exclusivity as the case maybe. Thus, the use of the alternative (e.g., “or”) should be understoodto mean either one, both, or any combination thereof of thealternatives. In addition, the composition of “and” and “or” whenrecited herein as “and/or” is intended to encompass an embodiment thatincludes all of the associated items or ideas and one or more otheralternative embodiments that include fewer than all of the associateditems or ideas.

Unless the context requires otherwise, throughout the specification andclaims that follow, the word “comprise” and synonyms and variantsthereof such as “have” and “include”, as well as variations thereof suchas “comprises” and “comprising” are to be construed in an open,inclusive sense, e.g., “including, but not limited to.” The term“consisting essentially of” limits the scope of a claim to the specifiedmaterials or steps, or to those that do not materially affect the basicand novel characteristics of the claimed invention.

Any headings used within this document are only being utilized toexpedite its review by the reader, and should not be construed aslimiting the invention or claims in any manner. Thus, the headings andAbstract of the Disclosure provided herein are for convenience only anddo not interpret the scope or meaning of the embodiments.

Where a range of values is provided herein, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges is also encompassed within the invention, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the invention.

For example, any concentration range, percentage range, ratio range, orinteger range provided herein is to be understood to include the valueof any integer within the recited range and, when appropriate, fractionsthereof (such as one tenth and one hundredth of an integer), unlessotherwise indicated. Also, any number range recited herein relating toany physical feature, such as polymer subunits, size or thickness, areto be understood to include any integer within the recited range, unlessotherwise indicated. As used herein, the term “about” means±20% of theindicated range, value, or structure, unless otherwise indicated.

All of the U.S. patents, U.S. patent application publications, U.S.patent applications, foreign patents, foreign patent applications andnon-patent publications referred to in this specification and/or listedin the Application Data Sheet, are incorporated herein by reference, intheir entirety. Such documents may be incorporated by reference for thepurpose of describing and disclosing, for example, materials andmethodologies described in the publications, which might be used inconnection with the presently described invention. The publicationsdiscussed herein and throughout the text are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the inventors are notentitled to antedate any referenced publication by virtue of priorinvention.

All patents, publications, scientific articles, web sites, and otherdocuments and materials referenced or mentioned herein are indicative ofthe levels of skill of those skilled in the art to which the inventionpertains, and each such referenced document and material is herebyincorporated by reference to the same extent as if it had beenincorporated by reference in its entirety individually or set forthherein in its entirety. Applicants reserve the right to physicallyincorporate into this specification any and all materials andinformation from any such patents, publications, scientific articles,web sites, electronically available information, and other referencedmaterials or documents.

In general, in the following claims, the terms used should not beconstrued to limit the claims to the specific embodiments disclosed inthe specification and the claims, but should be construed to include allpossible embodiments along with the full scope of equivalents to whichsuch claims are entitled. Accordingly, the claims are not limited by thedisclosure.

Furthermore, the written description portion of this patent includes allclaims. Furthermore, all claims, including all original claims as wellas all claims from any and all priority documents, are herebyincorporated by reference in their entirety into the written descriptionportion of the specification, and Applicants reserve the right tophysically incorporate into the written description or any other portionof the application, any and all such claims. Thus, for example, under nocircumstances may the patent be interpreted as allegedly not providing awritten description for a claim on the assertion that the precisewording of the claim is not set forth in haec verba in writtendescription portion of the patent.

The claims will be interpreted according to law. However, andnotwithstanding the alleged or perceived ease or difficulty ofinterpreting any claim or portion thereof, under no circumstances mayany adjustment or amendment of a claim or any portion thereof duringprosecution of the application or applications leading to this patent beinterpreted as having forfeited any right to any and all equivalentsthereof that do not form a part of the prior art.

Other nonlimiting embodiments are within the following claims. Thepatent may not be interpreted to be limited to the specific examples ornonlimiting embodiments or methods specifically and/or expresslydisclosed herein. Under no circumstances may the patent be interpretedto be limited by any statement made by any Examiner or any otherofficial or employee of the Patent and Trademark Office unless suchstatement is specifically and without qualification or reservationexpressly adopted in a responsive writing by Applicants.

What is claimed is:
 1. A composition comprising an additive in a polymerphase, wherein: a) the additive is soluble in a solvent; b) the polymerphase comprises an organic polymer and is essentially insoluble in thesolvent; c) the composition is a solid at temperatures below 25° C. anda viscous fluid with a Melt Flow Index of 2.5-30 g/10 min at atemperature above 50° C.; d) the composition has a weight percent of theadditive based on the weight of the composition and a weight percent ofthe polymer phase based on the weight of the composition, where the sumof the weight percent of the additive and the weight percent of thepolymer phase is greater than 90%; and e) the composition is in a formof a monofilament.
 2. The composition of claim 1 wherein themonofilament is an undrawn monofilament.
 3. The composition of claim 1wherein the monofilament has an orientation factor of less than 50%. 4.The composition of claim 1 wherein the monofilament has a diameter of1-5 mm.
 5. The composition of claim 1 wherein the additive comprises aninorganic salt.
 6. The composition of claim 1 wherein the additivecomprises a water-soluble organic compound.
 7. The composition of claim6 wherein the water-soluble organic compound is polyetheleneglycol. 8.The composition of claim 1 wherein the polymer phase comprises abioabsorbable polymer.
 9. The composition of claim 8 wherein thebioabsorbable polymer comprising segments selected from polyester,polyanhydride, poly(hydroxybutyrate) and polyether.
 10. The compositionof claim 1 wherein the polymer phase comprises a non-bioabsorbablepolymer.
 11. The composition of claim 10 wherein the non-bioabsorbablepolymer is selected from polyethylene, nylon, thermoplasticpolyurethane, polypropylene, polyetheretherketone, polyaryletherketoneand polyethylene terephthalate.
 12. The composition of claim 1 whereinthe weight percent of the additive in the composition is 1-60%.
 13. Thecomposition of claim 1 where the solvent is water, the additive issoluble in water and the polymer phase is insoluble in water.
 14. Thecomposition of claim 1 wherein the monofilament has a diameter of1.75±0.05 mm.
 15. The composition of claim 1 wherein the monofilamenthas a column buckling resistance of at least 1 Newton.
 16. A method offorming a composition in a form of a monofilament, the compositioncomprising an additive in a polymer phase, wherein the additive issoluble in a solvent, the polymer phase comprises an organic polymer andis essentially insoluble in the solvent, the composition is a solid attemperatures below 25° C. and a viscous fluid with a Melt Flow Index of2.5-30 g/10 min at a temperature above 50° C., the composition has aweight percent of the additive based on the weight of the compositionand a weight percent of the polymer phase based on the weight of thecomposition, where the sum of the weight percent of the additive and theweight percent of the polymer phase is greater than 90%, the methodcomprising: a) combining the additive and the polymer phase to form thecomposition; b) heating the composition to form a molten composition; c)extruding the molten composition to form an undrawn monofilament; and d)sterilizing the undrawn monofilament.
 17. The method of claim 16 whereinthe monofilament has an orientation factor of less than 50%.
 18. Themethod of claim 16 wherein the monofilament has a diameter of 1-5 mm.19. The method of claim 16 wherein the monofilament has a diameter of1.75±0.05 mm.
 20. The method of claim 16 wherein the monofilament has acolumn buckling resistance of at least 1 Newton.
 21. The method of claim16 wherein the additive comprises an inorganic salt.
 22. The method ofclaim 16 wherein the additive comprises a water-soluble organiccompound.
 23. The method of claim 22 wherein the water-soluble organiccompound is polyetheleneglycol.
 24. The method of claim 16 wherein thepolymer phase comprises a bioabsorbable polymer.
 25. The method of claim24 wherein the bioabsorbable polymer comprising segments selected frompolyester, polyanhydride, poly(hydroxybutyrate) and polyether.
 26. Themethod of claim 16 wherein the polymer phase comprises anon-bioabsorbable polymer.
 27. The method of claim 26 wherein thenon-bioabsorbable polymer is selected from polyethylene, nylon,thermoplastic polyurethane, polypropylene, polyetheretherketone,polyaryletherketone and polyethylene terephthalate.
 28. The method ofclaim 16 wherein the weight percent of the additive in the compositionis 1-60%.
 29. The method of claim 16 wherein the solvent is water, theadditive is soluble in water and the polymer phase is insoluble inwater.
 30. A method of forming an assembly comprising: a) providing acomposition in a molten form, the composition comprising an additive ina polymer phase, wherein the additive is soluble in a solvent, thepolymer phase comprises an organic polymer and is essentially insolublein the solvent, the composition is a solid at temperatures below 25° C.and a viscous fluid with a Melt Flow Index of 2.5-30 g/10 min at atemperature above 50° C., the composition has a weight percent of theadditive based on the weight of the composition and a weight percent ofthe polymer phase based on the weight of the composition, where the sumof the weight percent of the additive and the weight percent of thepolymer phase is greater than 90%; b) extruding the molten form of thecomposition to form an undrawn monofilament; c) winding the undrawnmonofilament onto a spool; and d) packaging the spool with monofilamentwound thereon.
 31. The method of claim 30 wherein the spool withmonofilament wound thereon is packaged in an air-tight container. 32.The method of claim 30 wherein the monofilament has an orientationfactor of less than 50%.
 33. The method of claim 30 wherein themonofilament has a diameter of 1-5 mm.
 34. The method of claim 30wherein the monofilament has a diameter of 1.75±0.05 mm.
 35. The methodof claim 30 wherein the monofilament has a column buckling resistance ofat least 1 Newton.
 36. The method of claim 30 wherein the additivecomprises an inorganic salt.
 37. The method of claim 30 wherein theadditive comprises a water-soluble organic compound.
 38. The method ofclaim 37 wherein the water-soluble organic compound ispolyetheleneglycol.
 39. The method of claim 30 wherein the polymer phasecomprises a bioabsorbable polymer.
 40. The method of claim 39 whereinthe bioabsorbable polymer comprising segments selected from polyester,polyanhydride, poly(hydroxybutyrate) and polyether.
 41. The method ofclaim 30 wherein the polymer phase comprises a non-bioabsorbablepolymer.
 42. The method of claim 41 wherein the non-bioabsorbablepolymer is selected from polyethylene, nylon, thermoplasticpolyurethane, polypropylene, polyetheretherketone, polyaryletherketoneand polyethylene terephthalate.
 43. The method of claim 30 wherein theweight percent of the additive in the composition is 1-60%.
 44. Themethod of claim 30 wherein the solvent is water, the additive is solublein water and the polymer phase is insoluble in water.
 45. A method ofadditive manufacturing, the method comprising: a) melting a solidcomposition to provide a molten composition, the molten compositioncomprising an additive and a polymer phase, wherein the additive issoluble in a solvent, the polymer phase comprises an organic polymer andis essentially insoluble in the solvent, the composition is a solid attemperatures below 25° C. and a viscous fluid with a Melt Flow Index of2.5-30 g/10 min at a temperature above 50° C., the composition has aweight percent of the additive based on the weight of the compositionand a weight percent of the polymer phase based on the weight of thecomposition, where the sum of the weight percent of the additive and theweight percent of the polymer phase is greater than 90%; b) performingadditive manufacturing to form an article from the molten composition;and c) contacting the article with a solvent, where the additive issoluble in the solvent, under conditions which at least partiallydissolves the additive but not the polymer phase, to form a porous formof the article.
 46. The method of claim 45 wherein the solvent dissolvesat least 50% of the additive.
 47. The method of claim 45 wherein thesolid composition is melted at a temperature of 50-450° C. to form themolten composition.
 48. The method of claim 45 wherein the additivemanufacturing method is fused filament fabrication (FFF).
 49. The methodof claim 45 wherein the porous form of the article comprises a pluralityof channels that run along the surface of the article in a longitudinaldirection compared to the longitudinal direction of a fibrous form ofthe molten composition created during the additive manufacturingprocess.
 50. The method of claim 45 further comprising sterilizing thearticle by a method selected from treatment with ethylene oxide, gamma,e-beam, dry heat and steam processes.
 51. The method of claim 45 furthercomprising removing solvent from the article such that any residualsolvent is less than one weight percent based on the weight of theporous form of the article.
 52. The method of claim 45 wherein themonofilament has an orientation factor of less than 50%.
 53. The methodof claim 45 wherein the monofilament has a diameter of 1-5 mm.
 54. Themethod of claim 45 wherein the monofilament has a diameter of 1.75±0.05mm.
 55. The method of claim 45 wherein the monofilament has a columnbuckling resistance of at least 1 Newton.
 56. The method of claim 45wherein the additive comprises an inorganic salt.
 57. The method ofclaim 45 wherein the additive comprises a water-soluble organiccompound.
 58. The method of claim 57 wherein the water-soluble organiccompound is polyetheleneglycol.
 59. The method of claim 45 wherein thepolymer phase comprises a bioabsorbable polymer.
 60. The method of claim59 wherein the bioabsorbable polymer comprising segments selected frompolyester, polyanhydride, poly(hydroxybutyrate) and polyether.
 61. Themethod of claim 45 wherein the polymer phase comprises anon-bioabsorbable polymer.
 62. The method of claim 61 wherein thenon-bioabsorbable polymer is selected from polyethylene, nylon,thermoplastic polyurethane, polypropylene, polyetheretherketone,polyaryletherketone and polyethylene terephthalate.
 63. The method ofclaim 45 wherein the weight percent of the additive in the compositionis 1-60%.
 64. The method of claim 45 wherein the solvent is water, theadditive is soluble in water and the polymer phase is insoluble inwater.
 65. A method of additive manufacturing, the method comprising: a)providing a composition comprising an additive in a polymer phase,wherein the additive is soluble in a solvent, the polymer phasecomprises an organic polymer and is essentially insoluble in thesolvent, the composition is a solid at temperatures below 25° C. and aviscous fluid with a Melt Flow Index of 2.5-30 g/10 min at a temperatureabove 50° C., the composition has a weight percent of the additive basedon the weight of the composition and a weight percent of the polymerphase based on the weight of the composition, where the sum of theweight percent of the additive and the weight percent of the polymerphase is greater than 90%; b) extruding the composition into amonofilament fiber; c) melting the monofilament fiber to provide amolten composition; d) performing additive manufacturing to form anarticle from the molten composition; e) contacting the article with asolvent, where the additive is soluble in the solvent, under conditionswhich at least partially dissolves the additive but not the polymerphase, to form a porous form of the article; and removing solvent fromthe porous form of the article such that any residual solvent is lessthan one weight percent based on the weight of the porous form of thearticle.
 66. The method of claim 65 wherein the monofilament has anorientation factor of less than 50%.
 67. The method of claim 65 whereinthe monofilament has a diameter of 1-5 mm.
 68. The method of claim 65wherein the monofilament has a diameter of 1.75±0.05 mm.
 69. The methodof claim 65 wherein the monofilament has a column buckling resistance ofat least 1 Newton.
 70. The method of claim 65 wherein the additivecomprises an inorganic salt.
 71. The method of claim 65 wherein theadditive comprises a water-soluble organic compound.
 72. The method ofclaim 71 wherein the water-soluble organic compound ispolyetheleneglycol.
 73. The method of claim 65 wherein the polymer phasecomprises a bioabsorbable polymer.
 74. The method of claim 73 whereinthe bioabsorbable polymer comprising segments selected from polyester,polyanhydride, poly(hydroxybutyrate) and polyether.
 75. The method ofclaim 65 wherein the polymer phase comprises a non-bioabsorbablepolymer.
 76. The method of claim 75 wherein the non-bioabsorbablepolymer is selected from polyethylene, nylon, thermoplasticpolyurethane, polypropylene, polyetheretherketone, polyaryletherketoneand polyethylene terephthalate.
 77. The method of claim 65 wherein theweight percent of the additive in the composition is 1-60%.
 78. Themethod of claim 65 wherein the solvent is water, the additive is solublein water and the polymer phase is insoluble in water.